【０００１】[0001]
【発明の属する技術分野】本発明はサイクリックヌクレ
オチドホスホジエステラーゼ阻害剤を有効成分として含
有する医薬製剤に関する。TECHNICAL FIELD The present invention relates to a pharmaceutical preparation containing a cyclic nucleotide phosphodiesterase inhibitor as an active ingredient.
【０００２】[0002]
【発明が解決しようとする課題】本発明はサイクリック
ヌクレオチドホスホジエステラーゼ阻害剤を有効成分と
して含有し、エリテマトーデス（以下、ＬＥと称す
る。）、特に全身性エリテマトーデス（以下、ＳＬＥと
称する。）、とりわけループス腎炎の治療または予防剤
として有用な医薬製剤を提供することを課題とする。The present invention contains a cyclic nucleotide phosphodiesterase inhibitor as an active ingredient and contains lupus erythematosus (hereinafter referred to as LE), particularly systemic lupus erythematosus (hereinafter referred to as SLE), especially lupus. An object is to provide a pharmaceutical preparation useful as a therapeutic or preventive agent for nephritis.
【０００３】[0003]
【課題を解決するための手段】本発明者等は、サイクリ
ックヌクレオチドホスホジエステラーゼ阻害剤がLE、特
にSLE、とりわけループス腎炎の予防または治療に有効
であることを見い出し、上記課題を解決し、本発明を完
成した。Means for Solving the Problems The present inventors have found that a cyclic nucleotide phosphodiesterase inhibitor is effective for the prevention or treatment of LE, especially SLE, especially lupus nephritis. Was completed.
【０００４】[0004]
【発明の実施の態様】本発明の製剤は、サイクリックヌ
クレオチドホスホジエステラーゼ（以下、サイクリック
ヌクレオチドPDEと称する。）阻害剤、好ましくはサイ
クリックグアノシンー３’,５’−一燐酸ホスホジエス
テラーゼ（以下、cGMP-PDEと称する。）阻害剤を有効成
分として含有するLEの予防または治療剤を製造し、これ
を人または動物に供することにより実施される。BEST MODE FOR CARRYING OUT THE INVENTION The preparation of the present invention comprises a cyclic nucleotide phosphodiesterase (hereinafter referred to as cyclic nucleotide PDE) inhibitor, preferably cyclic guanosine-3 ′, 5′-monophosphate phosphodiesterase (hereinafter cGMP). This is carried out by producing a prophylactic or therapeutic agent for LE containing an inhibitor as an active ingredient and providing it to humans or animals.
【０００５】本発明で使用するサイクリックヌクレオチ
ドPDE阻害剤としては、例えば、次の一般式（Ｉ）で表
される化合物がある。The cyclic nucleotide PDE inhibitors used in the present invention include, for example, compounds represented by the following general formula (I).
【０００６】[0006]
【化３】Embedded image
【０００７】［式中、Ｒ1は水素、ハロゲン、ニトロ、
カルボキシ、保護されたカルボキシ、アシル、シアノ、
ヒドロキシイミノ低級アルキル、オキソで置換されてい
てもよい低級アルケニル、または保護されたカルボキ
シ、カルボキシもしくはヒドロキシで置換されていても
よい低級アルキルであり、Ｒ2は水素、ハロゲン、低級
アルケニル、アシル、または保護されたカルボキシ、カ
ルボキシ、低級アルコキシもしくはヒドロキシで置換さ
れていてもよい低級アルキルであり、Ｒ3は低級アルケ
ニルまたは低級アルキルであって、ともに、(１)オキ
ソ、(２)ハロゲン、アリール、低級アルコキシ、低級ア
ルキレンジオキシ、シアノ、ニトロ、カルボキシ、保護
されたカルボキシ、アシル、およびアシルまたは保護さ
れたカルボキシで置換されていてもよいアミノからなる
群から選ばれた１個以上の置換基で置換されていてもよ
いアリール、ならびに(３)ハロゲンで置換されていても
よい複素環基からなる群から選ばれた１個以上の置換基
で置換されていてもよく、Ｒ4はカルボキシ、保護され
たカルボキシ、アシル、シアノ、ハロゲン、複素環基、
アシルもしくは保護されたカルボキシで置換されていて
もよいアミノ、または保護されたカルボキシ、カルボキ
シもしくはアシルで置換されていてもよい低級アルキル
であり、さらに、上記の意味に加えて、Ｒ1とＲ2 と
は、それらが結合している炭素原子とともに、オキソで
置換されていてもよい４〜７員炭素環式環をも表わすも
のである。］もしくはその医薬として許容しうる塩であ
る。Wherein R1 is hydrogen, halogen, nitro,
Carboxy, protected carboxy, acyl, cyano,
Hydroxyimino lower alkyl, lower alkenyl optionally substituted with oxo, or lower alkyl optionally substituted with protected carboxy, carboxy or hydroxy, wherein R2 is hydrogen, halogen, lower alkenyl, acyl, or R3 is lower alkenyl or lower alkyl which may be substituted with a protected carboxy, carboxy, lower alkoxy or hydroxy, and R3 is a group consisting of (1) oxo, (2) halogen, aryl, lower Substituted with one or more substituents selected from the group consisting of alkoxy, lower alkylenedioxy, cyano, nitro, carboxy, protected carboxy, acyl, and amino optionally substituted with acyl or protected carboxy Optionally substituted aryl, and (3) R4 may be substituted with one or more substituents selected from the group consisting of a heterocyclic group which may be substituted with halogen, and R4 is carboxy, protected carboxy, acyl, cyano, halogen, heterocyclic group. Group,
Amino optionally substituted with acyl or protected carboxy, or lower alkyl optionally substituted with protected carboxy, carboxy or acyl; furthermore, R1 and R2 Represents a 4- to 7-membered carbocyclic ring which may be substituted with oxo together with the carbon atom to which they are attached. Or a pharmaceutically acceptable salt thereof.
【０００８】式（Ｉ）の化合物は１か所以上の不斉中心
を有することもあり、それゆえ、それらは鏡像体または
ジアステレオマーとして存在しうる。さらに、アルケニ
ル基を含有する式（Ｉ）の若干の化合物は、シスまたは
トランス異性体として存在しうる。いずれの場合にも、
本発明はそれらの混合物および各個の異性体をともに包
含するものである。The compounds of formula (I) may have one or more asymmetric centers, and therefore they may exist as enantiomers or diastereomers. In addition, some compounds of Formula (I) containing an alkenyl group may exist as cis or trans isomers. In each case,
The present invention includes both the mixtures and the individual isomers.
【０００９】式（Ｉ）の化合物は互変異性体の形で存在
する場合もあり、本発明はそれらの混合物および各個の
互変異性体をともに包含するものである。式（Ｉ）の化
合物およびその塩は溶媒和物の形をとることもありうる
が、これも本発明の範囲に含まれる。溶媒和物として
は、好ましくは、水和物およびエタノール和物が挙げら
れる。The compounds of formula (I) may exist in tautomeric forms and the present invention includes both mixtures and individual tautomers. The compounds of formula (I) and salts thereof may be in the form of a solvate, which is also included in the scope of the present invention. The solvates preferably include hydrates and ethanol solvates.
【００１０】本発明で用いる化合物には生物学的研究に
適した式（Ｉ）の化合物の放射性同位体も含まれる。式
（Ｉ）の化合物の好ましい一群は、Ｒ1がシアノ、アシ
ル、またはヒドロキシで置換されていてもよい低級アル
キルであり、Ｒ2が水素、アシル、低級アルケニル、ま
たは低級アルコキシもしくはヒドロキシで置換されてい
てもよい低級アルキルであり、Ｒ3が、アリールまたは
複素環基で置換されたメチルであり、該アリールは、ハ
ロゲン、低級アルキレンジオキシ、保護されたカルボキ
シおよびカルボキシからなる群から選ばれた１個以上の
置換基で置換されてもよく、Ｒ4がアシル、シアノまた
は複素環基であり、上記の意味に加えて、Ｒ1とＲ2と
は、それらが結合している炭素原子とともに、オキソで
置換されていてもよい４〜７員炭素環式環を表わすこと
ができる。The compounds used in the present invention also include radioisotopes of the compounds of formula (I) which are suitable for biological studies. A preferred group of compounds of the formula (I) is that wherein R1 is lower alkyl optionally substituted by cyano, acyl or hydroxy and R2 is substituted by hydrogen, acyl, lower alkenyl or lower alkoxy or hydroxy. R3 is methyl substituted with an aryl or heterocyclic group, wherein said aryl is selected from the group consisting of halogen, lower alkylenedioxy, protected carboxy and carboxy. R4 may be an acyl, cyano or heterocyclic group, which may be substituted with one or more substituents, and in addition to the meanings given above, R1 and R2 together with the carbon atom to which they are attached , A 4- to 7-membered carbocyclic ring optionally substituted with oxo.
【００１１】式（Ｉ）の化合物のより好ましい一群は、
Ｒ1が低級アルキル、またはヒドロキシ、低級アルコキ
シもしくはアリールで置換されていてもよい低級アルカ
ノイルであり、Ｒ2が水素、低級アルケニル、または低
級アルコキシで置換されていてもよい低級アルキルであ
り、Ｒ3が、ハロゲンおよび低級アルキレンジオキシか
らなる群から選ばれた１個以上の置換基で置換されてい
てもよいベンジルであり、Ｒ4がアシル、シアノまたは
複素環基である。A more preferred group of compounds of the formula (I) is
R1 is lower alkyl or lower alkanoyl optionally substituted by hydroxy, lower alkoxy or aryl, R2 is hydrogen, lower alkenyl or lower alkyl optionally substituted by lower alkoxy, R3 Is benzyl which may be substituted with one or more substituents selected from the group consisting of halogen and lower alkylenedioxy, and R4 is an acyl, cyano or heterocyclic group.
【００１２】式（Ｉ）の化合物のとくに好ましい一群
は、Ｒ1が低級アルキル、またはヒドロキシ、低級アル
コキシもしくはアリールで置換されていてもよい低級ア
ルカノイルであり、Ｒ2が水素、低級アルケニル、また
は低級アルコキシで置換されていてもよい低級アルキル
であり、Ｒ3が、ハロゲンおよび低級アルキレンジオキ
シからなる群から選ばれた１個以上の置換基で置換され
ていてもよいベンジルであり、Ｒ4がA particularly preferred group of compounds of the formula (I) is that R1 is lower alkyl or lower alkanoyl optionally substituted by hydroxy, lower alkoxy or aryl and R2 is hydrogen, lower alkenyl or lower alkanoyl. R3 is lower alkyl optionally substituted with alkoxy, R3 is benzyl optionally substituted with one or more substituents selected from the group consisting of halogen and lower alkylenedioxy, and R4 is
【化４】でありＲ5は水素または低級アルキルであり、Ｒ6は水
素、ヒドロキシ、低級アルコキシ、アリールスルホニ
ル、複素環基、または低級シクロアルキルもしくは複素
環基で置換されていてもよい低級アルキルであり、上記
の意味に加えて、Ｒ5とＲ6とは、それらが結合している
窒素原子とともに、複素環基を表わすこともできる。式
（Ｉ）の化合物のとりわけ好ましい一群は、Ｒ1がアル
コキシで置換されていてもよい低級アルカノイルであ
り、Ｒ2が低級アルキルであり、Ｒ3が、ハロゲンおよび
低級アルキレンジオキシからなる群から選ばれた１個以
上の置換基で置換されていてもよいベンジルであり、Ｒ
4がカルバモイルである。Embedded image And R5 is hydrogen or lower alkyl; R6 is hydrogen, hydroxy, lower alkoxy, arylsulfonyl, a heterocyclic group, or a lower alkyl optionally substituted with a lower cycloalkyl or a heterocyclic group; R5 and R6 together with the nitrogen atom to which they are attached can also represent a heterocyclic group. A particularly preferred group of compounds of formula (I) is that wherein R1 is lower alkanoyl optionally substituted with alkoxy, R2 is lower alkyl, and R3 is halogen and lower alkylenedioxy. Benzyl optionally substituted with one or more selected substituents;
4 is carbamoyl.
【００１３】この発明で用いる化合物（Ｉ）またはその
塩は、次の諸方法により製造することができる。The compound (I) or a salt thereof used in the present invention can be produced by the following various methods.
【００１４】製造法１Manufacturing method 1
【化５】Embedded image
【００１５】製造法２Manufacturing method 2
【化６】Embedded image
【００１６】製造法３Manufacturing method 3
【化７】Embedded image
【００１７】製造法４Manufacturing method 4
【化８】Embedded image
【００１８】製造法５Manufacturing method 5
【化９】Embedded image
【００１９】製造法６Manufacturing method 6
【化１０】Embedded image
【００２０】製造法７Manufacturing method 7
【化１１】Embedded image
【００２１】製造法８Manufacturing method 8
【化１２】Embedded image
【００２２】製造法９Manufacturing method 9
【化１３】Embedded image
【００２３】製造法10Manufacturing method 10
【化１４】Embedded image
【００２４】製造法11Manufacturing method 11
【化１５】Embedded image
【００２５】製造法12Production method 12
【化１６】Embedded image
【００２６】製造法13Manufacturing method 13
【化１７】Embedded image
【００２７】製造法14Manufacturing method 14
【化１８】Embedded image
【００２８】製造法15Manufacturing method 15
【化１９】Embedded image
【００２９】製造法16Manufacturing method 16
【化２０】Embedded image
【００３０】製造法17Production method 17
【化２１】Embedded image
【００３１】製造法18Production method 18
【化２２】Embedded image
【００３２】製造法19Production method 19
【化２３】Embedded image
【００３３】製造法20Manufacturing method 20
【化２４】Embedded image
【００３４】製造法21Manufacturing method 21
【化２５】Embedded image
【００３５】製造法22Manufacturing method 22
【化２６】Embedded image
【００３６】製造法23Production method 23
【化２７】Embedded image
【００３７】製造法24Manufacturing method 24
【化２８】Embedded image
【００３８】ここに、Ｒ1〜Ｒ6は各々上に定義した通り
であり、Ｒ1aは、保護されたカルボキシまたはカルボキ
シで置換されていてもよい低級アルカノイルであり、Ｒ
1bは、保護されたカルボキシまたはカルボキシで置換さ
れていてもよい低級アルキルであり、Ｒ1cは低級アルケ
ノイル、アロイル、または保護されたカルボキシ、カル
ボシもしくはアリールで置換されていてもよい低級アル
カノイルであり、Ｒ1dはクロロアセチルであり、Ｒ1eは[0038] Here, R1 to R6 are as defined on each, R1a is protected carboxy or optionally substituted lower alkanoyl optionally substituted with carboxy, R
1b is substituted with protected carboxy or carboxy are also lower alkyl, R1c is lower alkenoyl, aroyl or protected carboxy, optionally substituted lower alkanoyl optionally substituted with Karuboshi or aryl, R1d is chloroacetyl, and R1e is
【化２９】であり、Ｒ1fは低級アルコキシで置換された低級アルカ
ノイルであり、Ｒ1gはヒドロキシで置換された低級アル
カノイルであり、Ｒ1hはハロゲンであり、Ｒ1iは、保護
されたカルボキシまたはカルボキシで置換されていても
よい低級アルキルであり、Ｒ1jは低級アルカノイルであ
り、Ｒ1kはヒドロキシイミノ低級アルキルであり、Ｒ2a
は保護されたカルボキシで置換された低級アルキルであ
り、Ｒ2bはカルボキシで置換された低級アルキルであ
り、Ｒ2cは１−ヒドロキシ低級アルキルであり、Ｒ2dは
低級アルカノイルであり、Embedded image R1f is lower alkanoyl substituted with lower alkoxy, R1g is lower alkanoyl substituted with hydroxy, R1h is halogen, R1i is a protected carboxy or R1j is lower alkanoyl, lower alkanoyl optionally substituted with carboxy, R1k is hydroxyimino lower alkyl, R2a
Is lower alkyl substituted with protected carboxy is, R2b is lower alkyl substituted with carboxy, R2c is 1-hydroxy-lower alkyl, R2d is lower alkanoyl,
【００３９】Ｒ3aは、低級アルケニルまたは低級アルキ
ルであって、ともにオキソで置換されていてもよく、と
もに保護されたカルボキシで置換されたアリールで置換
されているものであり、Ｒ3bは、低級アルケニルまたは
低級アルキルであって、ともにオキソで置換されていて
もよく、ともにカルボキシで置換されたアリールで置換
されているものであり、Ｒ3cは、低級アルケニルまたは
低級アルキルであって、ともにオキソで置換ささていて
もよく、ともに[0039] R3a is a lower alkenyl or lower alkyl, may be both substituted with oxo, which is substituted with aryl substituted with both protected carboxy, R3b is , Lower alkenyl or lower alkyl, both of which may be substituted by oxo, and both are substituted by aryl substituted by carboxy, R3c is lower alkenyl or lower alkyl; Both may be substituted with oxo,
【化３０】で置換されたアリールで置換されているものであり、Ｒ
3dは、低級アルケニルまたは低級アルキルであって、と
もにオキソで置換されていてもよく、ともにニトロで置
換されたアリールで置換されているものであり、Ｒ
3eは、低級アルケニルまたは低級アルキルであって、と
もにオキソで置換されていてもよく、ともにアミノで置
換されたアリールで置換されているものであり、Ｒ
3fは、低級アルケニルまたは低級アルキルであって、と
もにオキソで置換されていてもよく、ともにアミノで置
換されたアリールで置換されているものであり、Ｒ
3gは、低級アルケニルまたは低級アルキルであって、と
もにオキソで置換されていてもよく、アシル置換アミノ
で置換されたアリールで置換されているものであり、Embedded image Is substituted with an aryl substituted with
3d is lower alkenyl or lower alkyl, both optionally substituted by oxo, and both substituted by nitro-substituted aryl;
3e is lower alkenyl or lower alkyl, both of which may be substituted by oxo, and both of which are substituted by aryl substituted by amino;
3f is a lower alkenyl or lower alkyl, may be both substituted with oxo, which is substituted by aryl, both optionally substituted with amino, R
3g is lower alkenyl or lower alkyl, both of which may be substituted with oxo, and substituted with aryl substituted with acyl-substituted amino;
【００４０】Ｒ4aは保護されたカルボキシまたは保護さ
れたカルボキシで置換された低級アルキルであり、Ｒ4b
はカルボキシまたはカルボキシで置換された低級アルキ
ルであり、Ｒ4cは[0040] R4a is lower alkyl substituted with protected carboxy or protected carboxy, R4b
Is carboxy or lower alkyl substituted with carboxy, and R4c is
【化３１】またはEmbedded image Or
【化３２】で置換された低級アルキルであり、Ｒ7は水素、保護さ
れたカルボキシまたはEmbedded image Wherein R7 is hydrogen, protected carboxy or
【化３３】であり、Ｒ8はアシルであり、Ｒ9は低級アルキルであ
り、Ｘ1は離脱基であり、Ｘ2およびＸ3は各々Ｘ1と同意
義であり、ｎは１、２、３または４である。Embedded image R8 is acyl, R9 is lower alkyl, X1 is a leaving group, X2 and X3 are each equivalent to X1, and n is 1, 2, 3, or 4 It is.
【００４１】本明細書の上記および後記の記述において
本発明で使用される化合物の種々の定義の好適な例を、
以下に詳細に説明する。「低級」なる語は、とくに断わ
らない限り、１〜６個の炭素原子を有する基を意味する
ものとする。好適な「低級アルキル」ならびに「低級ア
ルコキシ」および「ヒドロキシイミノ低級アルキル」な
る表現における好適な低級アルキル部分は、メチル、エ
チル、プロピル、イソプロピル、ブチル、イソブチル、
第三級ブチル、ペンチル、ヘキシルなどの直鎖状または
分枝鎖状のＣ1ないしＣ6アルキルであり、なかでも好ま
しいのは、メチル、エチル、プロピル、ブチル、イソブ
チル、第三級ブチルなどのＣ1ないしＣ4低級アルキルで
ある。Preferred examples of the various definitions of the compounds used in the present invention in the description above and hereinafter are:
This will be described in detail below. The term "lower", unless otherwise indicated, shall mean a group having from 1 to 6 carbon atoms. Preferred "lower alkyl" and preferred lower alkyl moieties in the expressions "lower alkoxy" and "hydroxyimino lower alkyl" are methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
Linear or branched C1 to C6 alkyl such as tertiary butyl, pentyl, hexyl and the like, and particularly preferred are methyl, ethyl, propyl, butyl, isobutyl, tertiary butyl and the like. C1 -C4 lower alkyl.
【００４２】好適な「低級アルケニル」は、エテニル、
プロペニル（すなわちアリルまたは１−プロペニル）、
ブテニル、イソブテニルなどの直鎖状または分枝鎖状の
Ｃ2ないしＣ6アルケニルである。好適な「低級シクロア
ルキル」は、炭素原子数３ないし６のもの、たとえばシ
クロプロピル、シクロブチル、シクロペンチルなどであ
る。Preferred "lower alkenyl" is ethenyl,
Propenyl (ie allyl or 1-propenyl),
It is a linear or branched C2 -C6 alkenyl such as butenyl and isobutenyl. Preferred "lower cycloalkyl" are those having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and the like.
【００４３】好適な「アリール」ならびに「アリールス
ルホニル」、「アロイル」および「アル低級アルカノイ
ル」なる表現における好適なアリール部分としては、フ
ェニル、ナフチル、トリル、メシチル、キシリルなどが
挙げられる。好適な「ハロゲン」は、フルオロ、クロ
ロ、ブロモまたはヨードである。好適な「低級アルキレ
ンジオキシ」としては、メチレンジオキシ、エチレンジ
オキシなどである。Suitable aryl moieties in the expressions "aryl" and "arylsulfonyl", "aroyl" and "ar-lower alkanoyl" include phenyl, naphthyl, tolyl, mesityl, xylyl and the like. Preferred "halogens" are fluoro, chloro, bromo or iodo. Suitable "lower alkylenedioxy" includes methylenedioxy, ethylenedioxy and the like.
【００４４】好適な「保護されたカルボキシ」は、医薬
として許容しうるそして常用のものであって、エステル
化されたカルボキシなどの保護されたカルボキシであ
り、該エステル化されたカルボキシにおけるエステル部
分の具体例としては、アリールで置換されていてもよい
低級アルキル（たとえばメチル、エチル、プロピル、第
三級ブチル、ベンジルなど）が挙げられる。A preferred "protected carboxy" is pharmaceutically acceptable and conventional, which is a protected carboxy such as an esterified carboxy, wherein the ester moiety in the esterified carboxy is Specific examples include lower alkyl optionally substituted with aryl (eg, methyl, ethyl, propyl, tertiary butyl, benzyl, etc.).
【００４５】好適な「複素環基」は、窒素原子、硫黄原
子および酸素原子のうちから選ばれた少なくとも１個の
ヘテロ原子を含有するものであって、飽和または不飽和
の、単環式または多環式複素環基、たとえば (１) １ないし４個の窒素原子を含有する不飽和３ない
し７員（好ましくは５または６員）複素単環基、たとえ
ばピロリル、ピロリニル、イミダゾリル、ピラゾリル、
ピリジル、ピリミジニル、ピラジニル、ピリダジニル、
トリアゾリル［たとえば４Ｈ−１,２,４−トリアゾリ
ル、１Ｈ−１,２,３−トリアゾリル、２Ｈ−１,２,３−
トリアゾリルなど］、テトラゾリル［たとえば１Ｈ−テ
トラゾリル、２Ｈ−テトラゾリルなど］など； (２) １ないし４個の窒素原子を含有する飽和３ないし
７員（好ましくは５または６員）複素単環基、［たとえ
ばピロリジニル、イミダゾリジニル、ピペリジノ、ピペ
ラジニルなど］； (３) １ないし５個の窒素原子を含有する不飽和縮合複
素環基、たとえばインドリル、イソインドリル、インド
リジニル、ベンゾイミダゾリル、キノリル、イソキノリ
ル、インダゾリル、ベンゾトリアゾリル、テトラゾロピ
リダジニル［たとえばテトラゾロ［１,５−ｂ］ピリダ
ジニルなど］など； (４) １個の酸素原子を含有する不飽和３ないし７員(好
ましくは５または６員)複素単環基、たとえばピラニ
ル、フリルなど； (５) １ないし２個の硫黄原子を含有する不飽和３ない
し７員（好ましくは５または６員）複素単環基、たとえ
ばチエニルなど； (６) １ないし２個の酸素原子と１ないし３個の窒素原
子とを含有する不飽和３ないし７員（好ましくは５また
は６員）複素単環基、たとえばオキサゾリル、イソオキ
サゾリル、オキサジアゾリル［たとえば１,２,４−オキ
サジアゾリル、１,３,４−オキサジアゾリル、１,２,５
−オキサジアゾリルなど］など； (７) １ないし２個の酸素原子と１ないし３個の窒素原
子とを含有する飽和３ないし７員（好ましくは５または
６員）複素単環基、たとえばモルホリニルなど； (８) １ないし２個の酸素原子と１ないし３個の窒素原
子とを含有する不飽和縮合複素環基、たとえばベンゾオ
キサゾリル、ベンゾオキサジアゾリルなど； (９) １ないし２個の硫黄原子と１ないし３個の窒素原
子とを含有する不飽和３ないし７員（好ましくは５また
は６員）複素単環基、たとえばチアゾリル、チアジアゾ
リル［たとえば１,２,４−チアジアゾリル、１,３,４−
チアジアゾリル、１,２,５−チアジアゾリルなど］な
ど； (10) １ないし２個の硫黄原子と１ないし３個の窒素原
子とを含有する飽和３ないし７員（好ましくは５または
６員）複素単環基、たとえばチアゾリジニルなど； (11) １ないし２個の硫黄原子と１ないし３個の窒素原
子とを含有する不飽和縮合複素環基、たとえばベンゾチ
アゾリル、ベンゾチアジアゾリルなど； (12) １ないし２個の硫黄原子または１ないし２個の酸
素原子を含有する不飽和縮合複素環基、たとえばベンゾ
チオフェン、ベンゾフランなど；などを包含する。Preferred "heterocyclic groups" are those containing at least one heteroatom selected from nitrogen, sulfur and oxygen and are saturated or unsaturated, monocyclic or Polycyclic heterocyclic groups, such as (1) unsaturated 3- to 7-membered (preferably 5- or 6-membered) heteromonocyclic groups containing 1 to 4 nitrogen atoms, such as pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl,
Pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl,
Triazolyl [for example, 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-
Triazolyl, etc.], tetrazolyl [eg, 1H-tetrazolyl, 2H-tetrazolyl, etc.] and the like; (2) a saturated 3- to 7-membered (preferably 5- or 6-membered) heteromonocyclic group containing 1 to 4 nitrogen atoms, [ For example, pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl and the like]; (3) unsaturated fused heterocyclic group containing 1 to 5 nitrogen atoms, such as indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl , Tetrazolopyridazinyl [eg, tetrazolo [1,5-b] pyridazinyl and the like]; and (4) an unsaturated 3- to 7-membered (preferably 5- or 6-membered) heterocyclic ring containing one oxygen atom. Groups such as pyranyl, furyl and the like; (5) containing one or two sulfur atoms An unsaturated 3- to 7-membered (preferably 5- or 6-membered) heteromonocyclic group such as thienyl; (6) an unsaturated 3- to 3-unsaturated 3 to 7-membered group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms. 7-membered (preferably 5- or 6-membered) heterocyclic monocyclic groups such as oxazolyl, isoxazolyl, oxadiazolyl [eg 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5
And the like; (7) a saturated 3- to 7-membered (preferably 5- or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as morpholinyl; (8) Unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as benzoxazolyl and benzooxadiazolyl; (9) 1 to 2 sulfur Unsaturated 3- to 7-membered (preferably 5- or 6-membered) heteromonocyclic group containing an atom and 1 to 3 nitrogen atoms, such as thiazolyl, thiadiazolyl [eg 1,2,4-thiadiazolyl, 1,3, 4-
Thiadiazolyl, 1,2,5-thiadiazolyl, etc.] and the like; (10) a saturated 3- to 7-membered (preferably 5- or 6-membered) complex unit containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms. (11) Unsaturated fused heterocyclic groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, such as benzothiazolyl, benzothiadiazolyl, and the like; (12) 1 to 1 And unsaturated fused heterocyclic groups containing two sulfur atoms or one or two oxygen atoms, such as benzothiophene, benzofuran and the like.
【００４６】上記定義の「複素環基」は、更に、低級ア
ルキル、ヒドロキシ、ハロゲン、複素環基などの適当な
置換基で置換されていてもよい（たとえば３−ヒドロキ
シピロリジン、４−メチルピペラジン、４−ヒドロキシ
ピペリジン、１−メチルイミダゾール、４−（ピリミジ
ン−２−イル）ピペラジンなど）。好適な「アシル」
は、カルボン酸またはカルバミン酸から導かれた脂肪族
アシル、芳香族アシルまたはアリールで置換されていて
もよい脂肪族アシルである。The "heterocyclic group" as defined above may be further substituted with a suitable substituent such as lower alkyl, hydroxy, halogen, heterocyclic group (for example, 3-hydroxypyrrolidine, 4-methylpiperazine, 4-hydroxypiperidine, 1-methylimidazole, 4- (pyrimidin-2-yl) piperazine and the like). Preferred "acyl"
Is an aliphatic acyl derived from a carboxylic acid or a carbamic acid, an aliphatic acyl which may be substituted with an aromatic acyl or an aryl.
【００４７】脂肪族アシルとしては、 (１) ヒドロキシ、低級アルコキシ、カルボキシ、保護
されたカルボキシ、ハロゲン、低級アルキルチオ、複素
環チオ、オキソ、シクロ低級アルキル、複素環基などの
１個以上の適当な置換基で置換されていてもよい低級ア
ルカノイル（たとえばホルミル、アセチル、プロピオニ
ル、ブチリル、イソブチリル、ペンタノイル、ヘキサノ
イル、３,３−ジメチルブタノイル、３−ヒドロキシ−
３−メチルブタノイル、３−オキソブタノイル、３−メ
トキシカルボニルプロパノイル、３−カルボキシプロパ
ノイル、４−メトキシカルボニルブタノイル、４−カル
ボキシブタノイル、メチルチオアセチル、（１−メチル
イミダゾール−２−イル）チオアセチル、ヒドロキシア
セチル、メトキシアセチル、エトキシアセチル、３−メ
トキシブタノイル、クロロアセチル、モルホリノアセチ
ル、ピペリジニルアセチル、４−メチルピペリジン−１
−イルアセチル、４−ヒドロキシピペリジニル、ピロリ
ジニルアセチル、４−（ピリミジン−２−イル）ピペリ
ジニルアセチル、３−ヒドロキシピロリジニルアセチ
ル、オキソラン−４−イルアセチルなど）； (２) シクロ低級アルカンカルボニル（たとえばシクロ
プロピルカルボニル、シクロブチルカルボニル、シクロ
ペンチルカルボニル、シクロヘキシルカルボニルな
ど）； (３) 低級アルケノイル（たとえばアクリロイル、メタ
クリロイル、クロトノイル、３−メチルブタノイルな
ど）； (４)Examples of the aliphatic acyl include (1) one or more suitable groups such as hydroxy, lower alkoxy, carboxy, protected carboxy, halogen, lower alkylthio, heterocyclic thio, oxo, cyclo lower alkyl, and heterocyclic groups. Lower alkanoyl optionally substituted with a substituent (for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, hexanoyl, 3,3-dimethylbutanoyl, 3-hydroxy-
3-methylbutanoyl, 3-oxobutanoyl, 3-methoxycarbonylpropanoyl, 3-carboxypropanoyl, 4-methoxycarbonylbutanoyl, 4-carboxybutanoyl, methylthioacetyl, (1-methylimidazol-2-yl ) Thioacetyl, hydroxyacetyl, methoxyacetyl, ethoxyacetyl, 3-methoxybutanoyl, chloroacetyl, morpholinoacetyl, piperidinylacetyl, 4-methylpiperidine-1
-Ylacetyl, 4-hydroxypiperidinyl, pyrrolidinylacetyl, 4- (pyrimidin-2-yl) piperidinylacetyl, 3-hydroxypyrrolidinylacetyl, oxolan-4-ylacetyl, etc.); (2) cyclo-lower Alkanecarbonyl (eg, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, etc.); (3) lower alkenoyl (eg, acryloyl, methacryloyl, crotonoyl, 3-methylbutanoyl); (4)
【化３４】（ここに、Ｒ5は水素または低級アルキルであり、Ｒ6は
水素、ヒドロキシ、低級アルコキシ、アリールスルホニ
ル、複素環基、低級シクロアルキルまたは複素環基で置
換されていてもよい低級アルキルなどであり、上記の意
味に加えて、Ｒ5とＲ6とは、それらが結合している窒素
原子とともに複素環基を表わすこともできる）、たとえ
ばカルバモイル、Ｎ−メチルカルバモイル、Ｎ,Ｎ−ジ
メチルカルバモイル、Ｎ−エチルカルバモイル、Ｎ,Ｎ
−ジエチルカルバモイル、Ｎ−プロピルカルバモイル、
Ｎ−フェニルスルホニルカルバモイル、Ｎ−メトキシカ
ルバモイル、Ｎ−（テトラゾール−５−イル）カルバモ
イル、１−ピロリジニルカルボニル、ピペリジノカルボ
ニル、４−メチル−１−ピペラジニルカルボニル、４−
シクロヘキシル−１−ピペラジニルカルボニル、モルホ
リノカルボニル、４−チオモルホリニルカルボニルなど
が挙げられる。Embedded image (Where R5 is hydrogen or lower alkyl, R6 is hydrogen, hydroxy, lower alkoxy, arylsulfonyl, heterocyclic group, lower cycloalkyl or lower alkyl optionally substituted with a heterocyclic group, etc.) R5 and R6 , in addition to the above meanings, can also represent a heterocyclic group together with the nitrogen atom to which they are attached), for example carbamoyl, N-methylcarbamoyl, N, N-dimethylcarbamoyl, N-ethylcarbamoyl, N, N
-Diethylcarbamoyl, N-propylcarbamoyl,
N-phenylsulfonylcarbamoyl, N-methoxycarbamoyl, N- (tetrazol-5-yl) carbamoyl, 1-pyrrolidinylcarbonyl, piperidinocarbonyl, 4-methyl-1-piperazinylcarbonyl, 4-
Cyclohexyl-1-piperazinylcarbonyl, morpholinocarbonyl, 4-thiomorpholinylcarbonyl and the like can be mentioned.
【００４８】芳香族アシルとしては、ニトロなどの１個
以上の適当な置換基で置換されていてもよいアロイル
（たとえばベンゾイル、ナフトイル、ニトロベンゾイル
など）など挙げられる。アリールで置換された脂肪族ア
シルとしては、低級アルコキシなどの１個以上の適当な
置換基で置換されていてもよいアル低級アルカノイル
（たとえばフェニルアセチル、４−メトキシフェニルア
セチルなど）などが挙げられる。Examples of the aromatic acyl include aroyl (eg, benzoyl, naphthoyl, nitrobenzoyl, etc.) which may be substituted with one or more suitable substituents such as nitro. The aryl-substituted aliphatic acyl includes al-lower alkanoyl (eg, phenylacetyl, 4-methoxyphenylacetyl, etc.) which may be substituted with one or more suitable substituents such as lower alkoxy.
【００４９】好適な「アリールスルホニル」としては、
フェニルスルホニル、トシル、メトキシフェニルスルホ
ニルなどが挙げられる。好適な「離脱基」としては、ヒ
ドロキシ、ハロゲン、アシルオキシなどが挙げられ、こ
こに、ハロゲンおよびアシル部分は上に例示した通りで
ある。出発化合物（II）は、後記製造例と同様にして調
製する。Suitable "arylsulfonyl" includes:
Phenylsulfonyl, tosyl, methoxyphenylsulfonyl and the like. Suitable "leaving groups" include hydroxy, halogen, acyloxy and the like, wherein the halogen and acyl moieties are as exemplified above. The starting compound (II) is prepared in the same manner as in Production Examples described later.
【００５０】化合物（Ｉ）、（Ｉ−１）〜（Ｉ−36）お
よび（II）〜（VII）の好適な塩としては、塩基塩、た
とえばアルカリ金属塩（たとえばナトリウム塩、カリウ
ム塩など）、アルカリ土類金属塩（たとえばカルシウム
塩、マグネシウム塩など）、アンモニウム塩、アミン塩
（たとえばトリエチルアミン塩、Ｎ−ベンジル−Ｎ−メ
チルアミン塩など）および他の慣用の有機塩または酸付
加塩、たとえば塩酸塩、臭化水素酸塩、硫酸塩、重硫酸
塩、燐酸塩、燐酸水素塩、酢酸塩、安息香酸塩、コハク
酸塩、フマル酸塩、マレイン酸塩、乳酸塩、クエン酸
塩、酒石酸塩、グルコン酸塩、メタンスルホン酸塩、ベ
ンゼンスルホン酸塩、ｐ−トルエンスルホン酸塩など
の、医薬として許容しうる塩が挙げられる。Suitable salts of the compounds (I), (I-1) to (I-36) and (II) to (VII) include base salts, for example, alkali metal salts (for example, sodium salt, potassium salt and the like). , Alkaline earth metal salts (e.g., calcium salts, magnesium salts, etc.), ammonium salts, amine salts (e.g., triethylamine salts, N-benzyl-N-methylamine salts, etc.) and other conventional organic or acid addition salts, e.g. Hydrochloride, hydrobromide, sulfate, bisulfate, phosphate, hydrogen phosphate, acetate, benzoate, succinate, fumarate, maleate, lactate, citrate, tartaric acid Pharmaceutically acceptable salts such as salts, gluconates, methanesulfonates, benzenesulfonates, p-toluenesulfonates and the like.
【００５１】化合物（Ｉ）の製造法を、以下に詳細に説
明する。 製造法１ 化合物（Ｉ）またはその塩は、化合物（II）またはその
塩を化合物（III）またはその塩と反応させることによ
り製造できる。この反応は、通常、無機塩基または有機
塩基の存在下で実施する。The production method of compound (I) will be described in detail below. Production Method 1 Compound (I) or a salt thereof can be produced by reacting compound (II) or a salt thereof with compound (III) or a salt thereof. This reaction is usually performed in the presence of an inorganic base or an organic base.
【００５２】好適な無機塩基としては、アルカリ金属
［たとえばナトリウム、カリウムなど］、アルカリ金属
水酸化物［たとえば水酸化ナトリウム、水酸化カリウム
など］、アルカリ金属炭酸水素塩［たとえば炭酸水素ナ
トリウム、炭酸水素カリウムなど］、アルカリ金属炭酸
塩［たとえば炭酸ナトリウムなど］、アルカリ土類金属
炭酸塩［炭酸カルシウムなど］などが挙げられる。好適
な有機塩基としては、トリ（低級）アルキルアミン［た
とえばトリエチルアミン、Ｎ,Ｎ−ジイソプロピルエチ
ルアミンなど］、アルキルリチウム［たとえばメチルリ
チウム、ブチルリチウムなど］、リチウムジイソプロピ
ルアミド、リチウムヘキサメチルジシラジド、アルカリ
金属水素化物［たとえば水素化ナトリウム、水素化カリ
ウムなど］などが挙げられる。Suitable inorganic bases include alkali metals [eg, sodium, potassium, etc.], alkali metal hydroxides [eg, sodium hydroxide, potassium hydroxide, etc.], alkali metal bicarbonates [eg, sodium bicarbonate, bicarbonate] Potassium carbonate], an alkali metal carbonate [eg, sodium carbonate], an alkaline earth metal carbonate [calcium carbonate, etc.]. Suitable organic bases include tri (lower) alkylamines [eg, triethylamine, N, N-diisopropylethylamine, etc.], alkyllithiums [eg, methyllithium, butyllithium, etc.], lithium diisopropylamide, lithium hexamethyldisilazide, alkali Metal hydrides (eg, sodium hydride, potassium hydride, etc.).
【００５３】反応は、通常、慣用の溶媒、たとえば水、
アルコール［たとえばメタノール、エタノール、イソプ
ロピルアルコールなど］、テトラヒドロフラン、ジオキ
サン、トルエン、塩化メチレン、クロロホルム、Ｎ,Ｎ
−ジメチルホルムアミド、反応に悪影響を及ぼさないそ
の他の任意の有機溶媒、またはこれらの混合物中で実施
する。反応温度はとくに限定されないが、通常は、冷却
下ないし加温下で反応を実施する。The reaction is usually carried out using a conventional solvent such as water,
Alcohol [eg, methanol, ethanol, isopropyl alcohol, etc.], tetrahydrofuran, dioxane, toluene, methylene chloride, chloroform, N, N
-In dimethylformamide, any other organic solvent which does not adversely influence the reaction, or a mixture thereof. The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００５４】製造法２ 化合物（Ｉ−２）またはその塩は、化合物（Ｉ−１）を
脱エステル反応に付すことにより製造できる。反応は、
加水分解、還元などの常法に従って実施する。加水分解
は、塩基、酸、またはルイス酸とルイス塩基との組合せ
の存在下で実施するのが好ましい。好適な塩基として
は、無機塩基および有機塩基が挙げられる。好適な無機
塩基は、製造法１のところで例示したものと同じもので
ある。Production Method 2 Compound (I-2) or a salt thereof can be produced by subjecting compound (I-1) to a deesterification reaction. The reaction is
It is carried out according to a conventional method such as hydrolysis and reduction. The hydrolysis is preferably carried out in the presence of a base, an acid or a combination of a Lewis acid and a Lewis base. Suitable bases include inorganic and organic bases. Suitable inorganic bases are the same as those exemplified in Production Method 1.
【００５５】好適な有機塩基としては、トリ（低級）ア
ルキルアミン［たとえばトリメチルアミン、トリエチル
アミンなど］、ピコリン、１,５−ジアザビシクロ［４.
３.０］ノナ−５−エン、１,４−ジアザビシクロ［２.
２.２］オクタン、１,８−ジアザビシクロ［５.４.０］
ウンデカ−７−エンなどが挙げられる。好適な酸として
は、有機酸［たとえば蟻酸、酢酸、プロピオン酸、トリ
クロロ酢酸、トリフルオロ酢酸など］および無機酸［た
とえば塩酸、臭化水素酸、沃化水素酸、硫酸など］が挙
げられる。Suitable organic bases include tri (lower) alkylamines [eg, trimethylamine, triethylamine, etc.], picoline, 1,5-diazabicyclo [4.
3.0] Nona-5-ene, 1,4-diazabicyclo [2.
2.2] octane, 1,8-diazabicyclo [5.4.0]
And undec-7-ene. Suitable acids include organic acids (eg, formic acid, acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid, etc.) and inorganic acids (eg, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, etc.).
【００５６】加水分解は、ルイス酸とルイス塩基との組
合せの存在下でも実施できる。好適なルイス酸として
は、金属ハロゲン化物［たとえば塩化アルミニウム、臭
化アルミニウム、塩化チタン（IV）、塩化錫（IV）な
ど］、金属アルコキシド［たとえばチタン（IV）イソプ
ロポキシドなど］などが挙げられる。好適なルイス塩基
としては、低級アルキルチオール［たとえばエタンチオ
ール、エタンジチオールなど］、ジ低級アルキルスルフ
ィド［たとえばジメチルスルフィドなど］などが挙げら
れる。The hydrolysis can also be carried out in the presence of a combination of a Lewis acid and a Lewis base. Suitable Lewis acids include metal halides [eg, aluminum chloride, aluminum bromide, titanium (IV) chloride, tin (IV) chloride, etc.], metal alkoxides [eg, titanium (IV) isopropoxide, etc.], and the like. . Suitable Lewis bases include lower alkyl thiols [eg, ethanethiol, ethanedithiol, etc.], di-lower alkyl sulfides [eg, dimethyl sulfide, etc.], and the like.
【００５７】反応は、通常、水、アルコール［たとえば
メタノール、エタノールなど］、キシレン、ジエチレン
グリコールモノメチルエーテル、塩化メチレン、テトラ
ヒドロフラン、これらの混合物などの溶媒または反応に
悪影響を及ぼさないその他の任意の溶媒中で実施する。
液状の塩基または酸は、溶媒としても使用できる。反応
温度はとくに限定されないが、通常は、冷却下ないし加
温下で反応を実施する。The reaction is usually carried out in a solvent such as water, alcohol [eg, methanol, ethanol, etc.], xylene, diethylene glycol monomethyl ether, methylene chloride, tetrahydrofuran, a mixture thereof, or any other solvent which does not adversely influence the reaction. carry out.
Liquid bases or acids can also be used as solvents. The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００５８】還元は、４−ニトロベンジル、２−ヨード
エチル、２,２,２−トリクロロエチルなどのエステル部
分の脱離に好ましく適用できる。この脱離反応に適用で
きる還元法としては、化学還元および接触還元が挙げら
れる。化学還元に使用すべき好適な還元剤は、金属［た
とえば錫、亜鉛、鉄など］または金属化合物［たとえば
塩化クロム、酢酸クロムなど］と上に例示した有機酸ま
たは無機酸との組合せである。The reduction can be preferably applied to the elimination of an ester moiety such as 4-nitrobenzyl, 2-iodoethyl, 2,2,2-trichloroethyl and the like. Reduction methods applicable to this elimination reaction include chemical reduction and catalytic reduction. Suitable reducing agents to be used for chemical reduction are combinations of a metal [eg tin, zinc, iron etc.] or a metal compound [eg chromium chloride, chromium acetate etc.] with the organic or inorganic acids exemplified above.
【００５９】接触還元に使用すべき好適な触媒は、白金
触媒［たとえば白金炭素、酸化白金など］、パラジウム
触媒［たとえばパラジウム黒、酸化パラジウム、パラジ
ウム炭素など］または有機合成化学の分野で通常使用さ
れるその他の任意の触媒である。接触還元は、水素また
は水素供与体、たとえば蟻酸、蟻酸アンモニウム、シク
ロヘキセンなどの存在下で実施できる。Suitable catalysts to be used for the catalytic reduction are those usually used in the field of platinum catalysts (eg, platinum carbon, platinum oxide, etc.), palladium catalysts (eg, palladium black, palladium oxide, palladium carbon, etc.) or organic synthetic chemistry. Any other catalyst. The catalytic reduction can be carried out in the presence of hydrogen or a hydrogen donor such as formic acid, ammonium formate, cyclohexene and the like.
【００６０】還元は、通常、反応に悪影響を及ぼさない
慣用の溶媒、たとえば水、アルコール［たとえばメタノ
ール、エタノール、プロパノールなど］、Ｎ,Ｎ−ジメ
チルホルムアミド、またはこれらの混合物の中で実施す
る。なお、化学還元に使用する上記の酸が液状である場
合には、それらを溶媒としても使用できる。また、接触
還元に使用すべき好適な溶媒は、上記の溶媒およびジエ
チルエーテル、ジオキサン、テトラヒドロフランなどの
その他の慣用の溶媒またはそれらの混合物である。この
還元の反応温度はとくに限定されないが、通常は、冷却
下ないし加温下で反応を実施する。The reduction is usually carried out in a conventional solvent which does not adversely influence the reaction, for example, water, alcohol [eg methanol, ethanol, propanol, etc.], N, N-dimethylformamide, or a mixture thereof. When the above-mentioned acids used for chemical reduction are liquid, they can be used as a solvent. Suitable solvents to be used for the catalytic reduction are the above-mentioned solvents and other conventional solvents such as diethyl ether, dioxane, tetrahydrofuran or mixtures thereof. The reaction temperature for this reduction is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００６１】製造法３ 化合物（Ｉ−３）またはその塩は、化合物（Ｉ−２）も
しくはそのカルボキシ基における反応性誘導体、または
それらの塩を、化合物（IV）もしくはそのアミノ基にお
ける反応性誘導体、またはそれらの塩と、任意の周知の
操作法に従って反応させることにより、製造できる。Production Method 3 The compound (I-3) or a salt thereof is prepared by converting the compound (I-2) or a reactive derivative thereof at the carboxy group or a salt thereof from the compound (IV) or a reactive derivative thereof at the amino group thereof. Or a salt thereof, according to any well-known operation method.
【００６２】化合物（IV）のアミノ基における好適な反
応性誘導体としては、化合物（IV）とアルデヒド、ケト
ンなどのカルボニル化合物との反応によって形成される
シッフ塩基型イミノ体またはその互変異性体であるエナ
ミン体；化合物（IV）と塩化トリメチルシリル、Ｎ,Ｏ
−ビス（トリメチルシリル）アセトアミド、Ｎ−トリメ
チルシリルアセトアミドなどのシリル化試薬との反応に
よって形成されるシリル誘導体などが挙げられる。The preferred reactive derivative at the amino group of the compound (IV) is a Schiff base imino form formed by the reaction of the compound (IV) with a carbonyl compound such as an aldehyde or ketone or a tautomer thereof. A certain enamine; compound (IV) and trimethylsilyl chloride, N, O
And silyl derivatives formed by reaction with a silylating reagent such as -bis (trimethylsilyl) acetamide and N-trimethylsilylacetamide.
【００６３】化合物（Ｉ−２）の好適な反応性誘導体と
しては、酸塩化物、酸アジ化物、酸無水物、活性アミ
ド、活性エステルなどが挙げられる。好適な酸無水物と
しては、置換燐酸（たとえばジアルキル燐酸、フェニル
燐酸、ジフェニル燐酸、ジベンジル燐酸、ハロゲン化燐
酸など）、ジアルキル亜燐酸、硫酸、チオ硫酸、アルカ
ンスルホン酸（たとえばメタンスルホン酸、エタンスル
ホン酸など）、アルカン酸（たとえばピバル酸、ペンタ
ン酸、イソペンタン酸など）、芳香族カルボン酸（たと
えば安息香酸、クロロ安息香酸、フルオロ安息香酸、ニ
トロ安息香酸など）などの酸との混合酸無水物が挙げら
れる。Suitable reactive derivatives of the compound (I-2) include acid chlorides, acid azides, acid anhydrides, active amides, active esters and the like. Suitable acid anhydrides include substituted phosphoric acids (eg, dialkyl phosphoric acid, phenyl phosphoric acid, diphenyl phosphoric acid, dibenzyl phosphoric acid, halogenated phosphoric acid, etc.), dialkyl phosphorous acid, sulfuric acid, thiosulfuric acid, alkanesulfonic acid (eg, methanesulfonic acid, ethanesulfonic acid) Acid anhydrides), mixed acid anhydrides with acids such as alkanoic acids (eg, pivalic acid, pentanoic acid, isopentanoic acid), aromatic carboxylic acids (eg, benzoic acid, chlorobenzoic acid, fluorobenzoic acid, nitrobenzoic acid, etc.) Is mentioned.
【００６４】好適な活性アミドとしては、イミダゾイル
アミド、４−置換イミダゾイルアミド、ジメチルピラゾ
リルアミド、トリアゾリルアミド、テトラゾリルアミド
などである。好適な活性エステルは、ジメチルイミノメ
チル［(CH3)2N+＝CH−］エステル、ビニルエステル、プ
ロパルギルエステル、４−ニトロフェニルエステル、
２,４−ジニトロフェニルエステル、トリクロロフェニ
ルエステル、ペンタクロロフェニルエステル、ペンタフ
ルオロフェニルエステル、メタンスルホニルフェニルエ
ステル、フェニルチオエステル、ｐ−ニトロフェニルチ
オエステル、カルボキシメチルチオエステル、ピラニル
エステル、ピリジルエステル、８−キノリルチオエステ
ル、Ｎ−ヒドロキシ化合物（たとえばＮ,Ｎ−ジメチル
ヒドロキシルアミン、１−ヒドロキシ−２Ｈ−ピリド
ン、Ｎ−ヒドロキシスクシンイミド、Ｎ−ヒドロキシベ
ンゾトリアゾール、Ｎ−ヒドロキシフタルイミドなど）
とのエステルなどである。Suitable active amides include imidazoylamide, 4-substituted imidazoylamide, dimethylpyrazolylamide, triazolylamide, tetrazolylamide and the like. Suitable active esters include dimethyl imino-methyl[(CH 3) 2 N + = CH-] ester, vinyl ester, propargyl ester, 4-nitrophenyl ester,
2,4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, pentafluorophenyl ester, methanesulfonylphenyl ester, phenylthioester, p-nitrophenylthioester, carboxymethylthioester, pyranyl ester, pyridyl ester, 8-quinolylthioester , N-hydroxy compounds (eg, N, N-dimethylhydroxylamine, 1-hydroxy-2H-pyridone, N-hydroxysuccinimide, N-hydroxybenzotriazole, N-hydroxyphthalimide, etc.)
And the like.
【００６５】これらの反応性誘導体は、使用する化合物
（Ｉ−２）の種類に応じて、それらのうちから適宜選択
できる。化合物（Ｉ−２）を遊離の形で、またはその塩
の形で、反応に用いるときには、縮合剤の存在下で反応
を実施するのが好ましい。好適な縮合剤としては、カル
ボジイミド（たとえばＮ,Ｎ−ジシクロヘキシルカルボ
ジイミド、Ｎ−シクロヘキシル−Ｎ’−（４−ジエチル
アミノシクロヘキシル）カルボジイミド、Ｎ−エチル−
Ｎ’−（３−ジメチルアミノプロピル）カルボジイミド
またはその塩酸塩など）、ジフェニルホスフィン酸アジ
ド、ジフェニルホスフィン酸クロリド、ジエチルホスホ
リルシアニド、ビス（２−オキソ−３−オキサゾリジニ
ル）ホスフィン酸クロリド、Ｎ,Ｎ’−カルボニルジイ
ミダゾール、２−エトキシカルボニル−１,２−ジヒド
ロキノリン、シアヌル酸クロリドなどが挙げられる。These reactive derivatives can be appropriately selected from them according to the kind of the compound (I-2) to be used. When compound (I-2) is used in the free form or in the form of a salt thereof, the reaction is preferably carried out in the presence of a condensing agent. Suitable condensing agents include carbodiimides (eg, N, N-dicyclohexylcarbodiimide, N-cyclohexyl-N ′-(4-diethylaminocyclohexyl) carbodiimide, N-ethyl-
N '-(3-dimethylaminopropyl) carbodiimide or a hydrochloride thereof), diphenylphosphinic azide, diphenylphosphinic chloride, diethylphosphoryl cyanide, bis (2-oxo-3-oxazolidinyl) phosphinic chloride, N, N '-Carbonyldiimidazole, 2-ethoxycarbonyl-1,2-dihydroquinoline, cyanuric chloride and the like.
【００６６】反応を、アルカリ金属炭酸塩、トリ（低
級）アルキルアミン、ピリジン、Ｎ−（低級）アルキル
モルホリンなどの有機塩基または無機塩基の存在下で実
施することもできる。反応は、通常、慣用の溶媒、たと
えば水、アルコール［たとえばメタノール、エタノー
ル、イソプロピルアルコールなど］、テトラヒドロフラ
ン、ジオキサン、トルエン、塩化メチレン、クロロホル
ム、Ｎ,Ｎ−ジメチルホルムアミド、反応に悪影響を及
ぼさないその他の任意の有機溶媒またはこれらの混合物
中で実施する。反応温度はとくに限定されないが、通常
は、冷却下ないし加温下で反応を実施する。The reaction can also be carried out in the presence of an organic or inorganic base such as an alkali metal carbonate, a tri (lower) alkylamine, pyridine, N- (lower) alkylmorpholine. The reaction is usually carried out in a conventional solvent such as water, alcohol [eg, methanol, ethanol, isopropyl alcohol, etc.], tetrahydrofuran, dioxane, toluene, methylene chloride, chloroform, N, N-dimethylformamide, and other compounds which do not adversely affect the reaction. Performed in any organic solvent or mixture thereof. The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００６７】製造法４ 化合物（Ｉ−５）またはその塩は、化合物（Ｉ−４）ま
たはその塩を脱エステル反応に付すことにより製造でき
る。この脱エステル化は、製造法２と同様にして実施で
き、従って、使用すべき試薬および反応条件（たとえば
溶媒、反応温度など）としては、製造法２のそれらを挙
げることができる。Production Method 4 Compound (I-5) or a salt thereof can be produced by subjecting compound (I-4) or a salt thereof to a deesterification reaction. This deesterification can be carried out in the same manner as in Production Method 2. Accordingly, the reagents to be used and the reaction conditions (eg, solvent, reaction temperature, etc.) include those in Production Method 2.
【００６８】製造法５ 化合物（Ｉ−６）またはその塩は、化合物（Ｉ−５）も
しくはそのカルボキシ基における反応性誘導体、または
それらの塩を、化合物（IV）もしくはそのアミノ基にお
ける反応性誘導体、またはそれらの塩と反応させること
により製造できる。 この反応は、製造法３と同様にし
て実施でき、従って、使用すべき試薬および反応条件
（たとえば溶媒、反応温度など）としては、製造法３の
それらを挙げることができる。Preparation Method 5 Compound (I-6) or a salt thereof is prepared by converting compound (I-5) or a reactive derivative thereof at the carboxy group or a salt thereof from compound (IV) or a reactive derivative thereof at the amino group. , Or by reacting with a salt thereof. This reaction can be carried out in the same manner as in Production Method 3. Accordingly, the reagents to be used and the reaction conditions (eg, solvent, reaction temperature, etc.) include those in Production Method 3.
【００６９】製造法６ 化合物（Ｉ−８）またはその塩は、化合物（Ｉ−７）ま
たはその塩を還元剤と反応させることにより製造でき
る。好適な還元剤は、ジボラン、水素化硼素ナトリウ
ム、水素化アルミニウムリチウムなどである。反応は、
通常、慣用の溶媒、たとえばジエチルエーテル、テトラ
ヒドロフラン、反応に悪影響を及ぼさないその他の任意
の有機溶媒中で実施する。反応温度はとくに限定され
ず、通常、冷却下ないし加熱下で反応を実施する。Production Method 6 Compound (I-8) or a salt thereof can be produced by reacting compound (I-7) or a salt thereof with a reducing agent. Suitable reducing agents are diborane, sodium borohydride, lithium aluminum hydride and the like. The reaction is
Usually, the reaction is carried out in a conventional solvent such as diethyl ether, tetrahydrofuran or any other organic solvent which does not adversely influence the reaction. The reaction temperature is not particularly limited, and the reaction is usually carried out under cooling or heating.
【００７０】製造法７ 化合物（Ｉ−10）またはその塩は、化合物（Ｉ−９）ま
たはその塩をアシル化剤（Ｖ）と反応させることにより
製造できる。好適なアシル化剤（Ｖ）は、フリーデル・
クラフトアシル化反応に使用される慣用のもの、たとえ
ば酸ハロゲン化物［たとえば酸塩化物、酸臭化物な
ど］、酸無水物などが挙げられる。この反応は、ハロゲ
ン化アルミニウム［たとえば塩化アルミニウム、臭化ア
ルミニウムなど］、ハロゲン化チタン［たとえば四塩化
チタンなど］、ハロゲン化亜鉛（たとえば塩化亜鉛）、
三弗化硼素などのルイス酸の存在下で実施するのが好ま
しい。Production Method 7 Compound (I-10) or a salt thereof can be produced by reacting compound (I-9) or a salt thereof with an acylating agent (V). Suitable acylating agents (V) are Friedel
Examples thereof include conventional ones used in the kraft acylation reaction, for example, acid halides [eg, acid chlorides, acid bromides, etc.], acid anhydrides and the like. This reaction involves the reaction of an aluminum halide (eg, aluminum chloride, aluminum bromide, etc.), titanium halide (eg, titanium tetrachloride, etc.), zinc halide (eg, zinc chloride),
It is preferred to work in the presence of a Lewis acid such as boron trifluoride.
【００７１】反応は、通常、慣用の溶媒、たとえば二硫
化炭素、ジクロロエタン、テトラクロロメタン、ベンゼ
ン、反応に悪影響を及ぼさないその他の任意の有機溶媒
中で実施する。反応温度はとくに制限されず、通常、冷
却下ないし加熱下で反応を実施する。The reaction is usually carried out in a conventional solvent such as carbon disulfide, dichloroethane, tetrachloromethane, benzene or any other organic solvent which does not adversely influence the reaction. The reaction temperature is not particularly limited, and the reaction is usually carried out under cooling or heating.
【００７２】製造法８ 化合物（Ｉ−12）またはその塩は、化合物（Ｉ−11）ま
たはその塩をカルバモイル基における脱水反応に付すこ
とにより製造できる。脱水は、カルバモイル基を脱水し
てシアノ基としうる常法により実施でき、好適な脱水剤
は燐化合物（たとえば五酸化燐、五塩化燐、オキシ塩化
燐、三塩化ピロカテキル燐など）；塩化チオニル；また
はトリアリールホスフィン（たとえばトリフェニルホス
フィンなど）とクロロホルムまたは四塩化炭素との組合
せである。反応は、通常、慣用の溶媒、たとえば水、ア
ルコール［たとえばメタノール、エタノール、イソプロ
ピルアルコールなど］、テトラヒドロフラン、ジオキサ
ン、トルエン、塩化メチレン、クロロホルム、四塩化炭
素、Ｎ,Ｎ−ジメチルホルムアミド、反応に悪影響を及
ぼさないその他の任意の有機溶媒またはこれらの混合物
中で実施する。反応温度はとくに限定されないが、通常
は、冷却下ないし加温下で反応を実施する。Production Method 8 Compound (I-12) or a salt thereof can be produced by subjecting compound (I-11) or a salt thereof to a dehydration reaction at a carbamoyl group. Dehydration can be carried out by a conventional method in which a carbamoyl group can be dehydrated to a cyano group, and suitable dehydrating agents are phosphorus compounds (for example, phosphorus pentoxide, phosphorus pentachloride, phosphorus oxychloride, pyrocatechyl phosphorus trichloride, etc.); thionyl chloride; Or a combination of a triarylphosphine (eg, triphenylphosphine, etc.) with chloroform or carbon tetrachloride. The reaction is usually carried out in a conventional solvent such as water, alcohol [eg, methanol, ethanol, isopropyl alcohol, etc.], tetrahydrofuran, dioxane, toluene, methylene chloride, chloroform, carbon tetrachloride, N, N-dimethylformamide, which adversely affects the reaction. It is carried out in any other organic solvent which does not affect or a mixture thereof. The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００７３】製造法９ 化合物（Ｉ−13）またはその塩は、化合物（Ｉ−12）ま
たはその塩をアジド化合物と反応させることにより製造
できる。好適なアジド化合物は、アジ化アルカリ金属
［たとえばアジ化ナトリウム、アジ化カリウムなど］、
アジ化アルカリ土類金属［たとえばアジ化カルシウムな
ど］、アジ化アルミニウム、アジ化水素、アジ化トリメ
チル錫などである。反応は、ハロゲン化アンモニウム
［たとえば塩化アンモニウム、臭化アンモニウムな
ど］、ハロゲン化低級アルキルアンモニウム［たとえば
塩化トリメチルアンモニウム、塩化トリエチルアンモニ
ウムなど］などの存在下で実施するのが好ましい。Production Method 9 Compound (I-13) or a salt thereof can be produced by reacting compound (I-12) or a salt thereof with an azide compound. Suitable azide compounds include alkali metal azides [eg, sodium azide, potassium azide, etc.],
Alkaline earth metal azide [eg, calcium azide]; aluminum azide; hydrogen azide; trimethyltin azide; The reaction is preferably carried out in the presence of an ammonium halide [eg, ammonium chloride, ammonium bromide, etc.], a lower alkyl ammonium halide [eg, trimethylammonium chloride, triethylammonium chloride, etc.].
【００７４】反応は、通常、慣用の溶媒、たとえばテト
ラヒドロフラン、ジオキサン、Ｎ,Ｎ−ジメチルホルム
アミドまたは反応に悪影響を及ぼさないその他の任意の
有機溶媒中で実施する。反応温度はとくに限定されない
が、通常は、加温下ないし加熱下で反応を実施する。The reaction is usually carried out in a conventional solvent such as tetrahydrofuran, dioxane, N, N-dimethylformamide or any other organic solvent which does not adversely influence the reaction. The reaction temperature is not particularly limited, but usually the reaction is carried out under heating or under heating.
【００７５】製造法10 化合物（Ｉ−15）またはその塩は、化合物（Ｉ−14）ま
たはその塩を脱エステル反応に付すことにより製造でき
る。この脱エステルは製造法２と同様にして実施でき、
従って、使用すべき試薬および反応条件（たとえば溶
媒、反応温度など）としては、製造法２のそれらを挙げ
ることができる。Production Method 10 Compound (I-15) or a salt thereof can be produced by subjecting compound (I-14) or a salt thereof to a deesterification reaction. This deesterification can be carried out in the same manner as in Production Method 2,
Accordingly, the reagents to be used and the reaction conditions (eg, solvent, reaction temperature, etc.) include those of Production Method 2.
【００７６】製造法11 化合物（Ｉ−16）またはその塩は、化合物（Ｉ−15）ま
たはその塩を分子内アシル化反応に付すことにより製造
できる。この分子内アシル化反応は製造法７と同様にし
て実施でき、従って、使用すべき試薬および反応条件
（たとえば溶媒、反応温度など）としては、製造法７の
それらを挙げることができる。Production Method 11 Compound (I-16) or a salt thereof can be produced by subjecting compound (I-15) or a salt thereof to an intramolecular acylation reaction. This intramolecular acylation reaction can be carried out in the same manner as in Production Method 7. Therefore, the reagents to be used and the reaction conditions (eg, solvent, reaction temperature, etc.) include those in Production Method 7.
【００７７】製造法12 化合物（Ｉ−18）またはその塩は、化合物（Ｉ−17）ま
たはその塩を化合物（IV）と反応させることにより製造
できる。この反応は、製造法１のところで例示した有機
塩基または無機塩基および／またはアルキル金属沃化物
（たとえば沃化ナトリウム、沃化カリウムなど）の存在
下で実施するのが好ましい。反応は、通常、水、テトラ
ヒドロフラン、ジオキサン、Ｎ,Ｎ−ジメチルホルムア
ミドなどの溶媒または反応に悪影響を及ぼさないその他
の任意の溶媒中で実施する。反応温度はとくに限定され
ないが、通常は、室温または加温ないし加熱下で反応を
実施する。Production Method 12 Compound (I-18) or a salt thereof can be produced by reacting compound (I-17) or a salt thereof with compound (IV). This reaction is preferably carried out in the presence of the organic or inorganic base exemplified in Production Method 1 and / or an alkyl metal iodide (eg, sodium iodide, potassium iodide, etc.). The reaction is usually performed in a solvent such as water, tetrahydrofuran, dioxane, N, N-dimethylformamide or any other solvent that does not adversely influence the reaction. The reaction temperature is not particularly limited, but the reaction is usually carried out at room temperature or under heating or heating.
【００７８】製造法13 化合物（Ｉ−19）またはその塩は、化合物（Ｉ−９）ま
たはその塩をホルミル化剤と反応させることにより製造
できる。好適なホルミル化剤は、Ｎ,Ｎ−ジメチルホル
ムアミド；（CH3)2N+＝CHCl・Cl2PO2- （Ｎ,Ｎ−ジメチ
ルホルムアミドとオキシ塩化燐、ホスゲンなどとの反応
により調製されるいわゆるビルスマイヤー試薬）などで
ある。ホルミル化剤がＮ,Ｎ−ジメチルホルムアミドで
あるときには、低級アルキルアルカリ金属［たとえばｎ
−ブチルリチウム、臭化エチルマグネシウムなど］など
の存在下で反応を実施するのが好ましい。Production Method 13 Compound (I-19) or a salt thereof can be produced by reacting compound (I-9) or a salt thereof with a formylating agent. Suitable formylating agents include, N,N-dimethylformamide; (CH 3) 2 N + = CHCl · Cl 2 PO 2 - are prepared (N, N-dimethylformamide and phosphorus oxychloride by reaction with such phosgene So-called Vilsmeier reagent). When the formylating agent is N, N-dimethylformamide, a lower alkyl alkali metal [for example, n
-Butyllithium, ethylmagnesium bromide, etc.].
【００７９】反応は、通常、ジオキサン、テトラヒドロ
フラン、Ｎ,Ｎ−ジメチルホルムアミド、塩化メチレ
ン、クロロホルムなどの溶媒または反応に悪影響を及ぼ
さないその他の任意の有機溶媒中で実施する。反応温度
はとくに限定されず、通常、冷却下ないし加熱下で反応
を実施する。The reaction is usually carried out in a solvent such as dioxane, tetrahydrofuran, N, N-dimethylformamide, methylene chloride, chloroform or any other organic solvent which does not adversely influence the reaction. The reaction temperature is not particularly limited, and the reaction is usually carried out under cooling or heating.
【００８０】製造法14 化合物（Ｉ−20）またはその塩は、化合物（Ｉ−19）ま
たはその塩を酸化反応に付すことにより製造できる。酸
化は、ホルミル基を酸化してカルボキシ基としうる常法
により実施する。好適な酸化剤は、過沃素酸塩（たとえ
ば過沃素酸ナトリウム、過沃素酸カリウムなど）などの
酸素酸、過安息香酸（たとえば過安息香酸、ｍ−クロロ
過安息香酸など）などの過酸、過マンガン酸カリウム、
クロム酸、次亜塩素酸ナトリウムなどである。Production Method 14 Compound (I-20) or a salt thereof can be produced by subjecting compound (I-19) or a salt thereof to an oxidation reaction. The oxidation is carried out by a conventional method which can oxidize a formyl group to a carboxy group. Suitable oxidizing agents are oxyacids such as periodate (eg, sodium periodate, potassium periodate, etc.), peracids such as perbenzoic acid (eg, perbenzoic acid, m-chloroperbenzoic acid, etc.), Potassium permanganate,
Chromic acid, sodium hypochlorite and the like.
【００８１】反応は、通常、慣用の溶媒、たとえば水、
アルコール（たとえばメタノール、エタノール、イソプ
ロピルアルコールなど）、テトラヒドロフラン、ジオキ
サン、ジクロロメタン、二塩化エチレン、クロロホル
ム、Ｎ,Ｎ−ジメチルホルムアミド、Ｎ,Ｎ−ジメチルア
セトアミド、反応に悪影響を及ぼさないその他の任意の
有機溶媒中で実施する。これらの溶媒のうち、親水性の
溶媒は、水との混合物として用いてもよい。反応温度は
とくに限定されず、通常、冷却下ないし加熱下で反応を
実施する。The reaction is usually carried out using a conventional solvent, for example, water,
Alcohols (eg, methanol, ethanol, isopropyl alcohol, etc.), tetrahydrofuran, dioxane, dichloromethane, ethylene dichloride, chloroform, N, N-dimethylformamide, N, N-dimethylacetamide, and any other organic solvent that does not adversely affect the reaction Implemented in Among these solvents, the hydrophilic solvent may be used as a mixture with water. The reaction temperature is not particularly limited, and the reaction is usually carried out under cooling or heating.
【００８２】製造法15 化合物（Ｉ−22）またはその塩は、化合物（Ｉ−21）ま
たはその塩を転位反応に付すことにより製造できる。カ
ルボキシ基を保護されたカルボキシまたはアシルで置換
されていてもよいアミノ基（たとえば低級アルキルで置
換されたカルバモイルなど）に変換しうる転位反応とし
ては、クルチウス転位、ホフマン反応、シュミット反応
またはそれらの変法などの条件が挙げられる。たとえ
ば、クルチウス転位は、酸アジドの形成、酸アジドのイ
ソシアナートおよび窒素への分解およびイソシアナート
の水、アルコールまたはアミンとの反応からなり、それ
ぞれアミン、ウレタンまたは尿素を与える。Production Method 15 Compound (I-22) or a salt thereof can be produced by subjecting compound (I-21) or a salt thereof to a rearrangement reaction. The rearrangement reaction that can convert a carboxy group to an amino group optionally substituted by protected carboxy or acyl (such as carbamoyl substituted by lower alkyl) includes Curtius rearrangement, Hoffman reaction, Schmidt reaction, or a modification thereof. Conditions such as the law. For example, the Curtius rearrangement consists of the formation of an acid azide, the decomposition of an acid azide to isocyanates and nitrogen, and the reaction of isocyanates with water, alcohols or amines to give amines, urethanes or ureas, respectively.
【００８３】酸アジ化物は、対応する酸ヒドラジドを亜
硝酸で処理する，対応する酸塩化物をアルカリ金属アジ
化物で処理する、カルボン酸をジフェニルホスホリルア
ジドで処理するなどの方法により調製できる。酸アジ化
物は、不活性溶媒（たとえばトルエン、ジクロロメタン
など）中で転位させることができ、イソシアナートを単
離することができ、または、中間体イソシアナートと反
応するアルコール、アミンなどの試薬の存在下で転位さ
せて、ウレタンまたは尿素を生成させることができる。
イソシアナート、ウレタンまたは尿素の加水分解によっ
て、アミンまたはその塩を得ることができる。反応温度
はとくに限定されないが、通常は、冷却下ないし加温下
で反応を実施する。The acid azide can be prepared by a method such as treating the corresponding acid hydrazide with nitrous acid, treating the corresponding acid chloride with an alkali metal azide, treating the carboxylic acid with diphenylphosphoryl azide, and the like. The acid azide can be rearranged in an inert solvent (eg, toluene, dichloromethane, etc.), to isolate the isocyanate, or to the presence of reagents such as alcohols, amines, etc. that react with the intermediate isocyanate. Rearrangement can produce urethane or urea.
Amines or salts thereof can be obtained by hydrolysis of isocyanates, urethanes or ureas. The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００８４】製造法16 化合物（Ｉ−24）またはその塩は、化合物（Ｉ−23）も
しくはそのアミノ基における反応性誘導体、またはそれ
らの塩を化合物（VI）またはその塩もしくは化合物（VI
I）またはその塩と反応させることにより製造できる。
化合物（VI）として遊離酸を用いるときには、製造法３
のところで例示した縮合剤の存在下で反応を実施するの
が好ましい。反応は、通常、慣用の溶媒、たとえば水、
アルコール［たとえばメタノール、エタノール、イソプ
ロピルアルコールなど］、テトラヒドロフラン、ジオキ
サン、トルエン、塩化メチレン、クロロホルム、Ｎ,Ｎ
−ジメチルホルムアミド、反応に悪影響を及ぼさないそ
の他の任意の有機溶媒またはそれらの混合物中で実施す
る。反応温度はとくに限定されないが、通常は、冷却下
ないし加温下で反応を実施する。Production method 16 Compound (I-24) or a salt thereof is prepared by converting compound (I-23) or a reactive derivative at the amino group thereof or a salt thereof to compound (VI) or a salt or compound (VI
It can be produced by reacting with I) or a salt thereof.
When a free acid is used as the compound (VI), the production method 3
The reaction is preferably carried out in the presence of the condensing agent exemplified above. The reaction is usually carried out in a customary solvent such as water,
Alcohol [eg, methanol, ethanol, isopropyl alcohol, etc.], tetrahydrofuran, dioxane, toluene, methylene chloride, chloroform, N, N
Carried out in dimethylformamide, any other organic solvent which does not adversely influence the reaction or a mixture thereof. The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００８５】製造法17 化合物（Ｉ−26）またはその塩は、化合物（Ｉ−25）ま
たはその塩を還元に付すことにより製造できる。本還元
は、化学還元、接触還元などにより実施する。化学還元
に使用すべき好適な還元剤は、金属［たとえば錫、亜
鉛、鉄など］または金属化合物［たとえば塩化クロム、
酢酸クロムなど］と有機酸または無機酸［たとえば蟻
酸、酢酸、プロピオン酸、トリフルオロ酢酸、ｐ−トル
エンスルホン酸、塩酸、臭化水素酸など］との組合せで
ある。Production Method 17 Compound (I-26) or a salt thereof can be produced by subjecting compound (I-25) or a salt thereof to reduction. This reduction is performed by chemical reduction, catalytic reduction, or the like. Suitable reducing agents to be used for chemical reduction include metals [eg, tin, zinc, iron, etc.] or metal compounds [eg, chromium chloride,
Chromium acetate, etc.] and an organic or inorganic acid [for example, formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, etc.].
【００８６】接触還元に使用すべき好適な触媒は、白金
触媒［たとえば白金、白金黒、酸化白金など］、パラジ
ウム触媒［たとえばパラジウム黒、酸化パラジウム、パ
ラジウム炭素など］、ニッケル触媒［たとえば還元ニッ
ケル、酸化ニッケル、ラネーニッケルなど］、コバルト
触媒［たとえば還元コバルト、ラネーコバルトなど］、
鉄触媒［たとえば還元鉄、ラネー鉄など］、銅触媒［た
とえば還元銅、ラネー銅、ウルマン銅など］などの慣用
のものである。Suitable catalysts to be used for the catalytic reduction include platinum catalysts (eg, platinum, platinum black, platinum oxide, etc.), palladium catalysts (eg, palladium black, palladium oxide, palladium carbon, etc.), nickel catalysts (eg, reduced nickel, Nickel oxide, Raney nickel, etc.], a cobalt catalyst [eg, reduced cobalt, Raney cobalt, etc.],
Conventional catalysts such as iron catalysts (eg, reduced iron, Raney iron, etc.) and copper catalysts (eg, reduced copper, Raney copper, Ullman copper, etc.).
【００８７】還元は、通常、反応に悪影響を及ぼさない
慣用の溶媒、たとえば水、アルコール［たとえばメタノ
ール、エタノール、プロパノールなど］、Ｎ,Ｎ−ジメ
チルホルムアミドまたはこれらの混合物中で実施する。
なお、化学還元に使用する上記の酸が液状である場合に
は、それらを溶媒として使用することもできる。また、
接触還元に使用すべき好適な溶媒は、上記の溶媒および
ジエチルエーテル、塩化メチレン、ジオキサン、テトラ
ヒドロフランなどのその他の溶媒もしくはそれらの混合
物である。この還元の反応温度はとくに限定されない
が、通常は、冷却下ないし加温下で反応を実施する。The reduction is usually carried out in a conventional solvent which does not adversely influence the reaction, for example, water, alcohol [eg methanol, ethanol, propanol, etc.], N, N-dimethylformamide or a mixture thereof.
When the above-mentioned acids used for chemical reduction are liquid, they can also be used as a solvent. Also,
Suitable solvents to be used for the catalytic reduction are the abovementioned solvents and other solvents such as diethyl ether, methylene chloride, dioxane, tetrahydrofuran or mixtures thereof. The reaction temperature for this reduction is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００８８】製造法18 化合物（Ｉ−28）またはその塩は、化合物（Ｉ−27）ま
たはその塩をエーテル結合開裂反応に付すことにより製
造できる。エーテル結合の開裂は、ルイス酸を含む酸
［たとえば塩酸、臭化水素酸、沃化水素酸、三臭化硼
素、三塩化硼素など］、沃化トリ（低級）アルキルシリ
ル［たとえば沃化トリメチルシリルなど］の存在下で、
または有機合成の分野で常用されるその他の任意の方法
で実施する。反応は、通常、水、酢酸、塩化メチレン、
テトラヒドロフラン、これらの混合物などの溶媒または
反応に悪影響を及ぼさないその他の任意の溶媒中で実施
する。反応温度はとくに限定されず、通常、冷却ないし
加熱下で反応を実施する。Production Method 18 Compound (I-28) or a salt thereof can be produced by subjecting compound (I-27) or a salt thereof to an ether bond cleavage reaction. Cleavage of the ether bond may be carried out by using an acid containing a Lewis acid [eg, hydrochloric acid, hydrobromic acid, hydroiodic acid, boron tribromide, boron trichloride, etc.], tri (lower) alkylsilyl iodide [eg trimethylsilyl iodide, etc.] ] In the presence of
Alternatively, the reaction is carried out by any other method commonly used in the field of organic synthesis. The reaction is usually carried out with water, acetic acid, methylene chloride,
The reaction is performed in a solvent such as tetrahydrofuran, a mixture thereof, or any other solvent that does not adversely influence the reaction. The reaction temperature is not particularly limited, and the reaction is usually carried out under cooling or heating.
【００８９】製造法19 化合物（Ｉ−30）またはその塩は、化合物（Ｉ−29）ま
たはその塩を酸化に付すことにより製造できる。この酸
化反応は、第二級アルコールをケトンに酸化しうる有機
化学の分野で常用される一般的操作法に従って実施で
き、好適な酸化剤は、たとえば六価クロム（ＣｒVI）誘
導体（たとえば三酸化クロム、重クロム酸ナトリウム、
三酸化クロム−ジピリジン錯体など）または七価マンガ
ン（ＭｎVII）誘導体（たとえば過マンガン酸カリウ
ム、二酸化マンガンなど）である。反応は、通常、慣用
の溶媒、たとえば水、テトラヒドロフラン、ジオキサ
ン、トルエン、塩化メチレン、クロロホルム、Ｎ,Ｎ−
ジメチルホルムアミド、アセトン、反応に悪影響を及ぼ
さないその他の任意の有機溶媒またはこれらの混合物中
で実施する。反応温度はとくに限定されないが、通常
は、冷却下ないし加温下で反応を実施する。Production Method 19 Compound (I-30) or a salt thereof can be produced by subjecting compound (I-29) or a salt thereof to oxidation. This oxidation reaction can be carried out according to general procedures commonly used in the field of organic chemistry which can oxidize secondary alcohols to ketones, and suitable oxidizing agents include, for example, hexavalent chromium (CrVI ) derivatives (for example, trioxide Chromium, sodium bichromate,
Chromium trioxide-dipyridine complex) or a heptavalent manganese (MnVII ) derivative (eg, potassium permanganate, manganese dioxide, etc.). The reaction is usually carried out in a conventional solvent such as water, tetrahydrofuran, dioxane, toluene, methylene chloride, chloroform, N, N-
The reaction is carried out in dimethylformamide, acetone, any other organic solvent which does not adversely influence the reaction, or a mixture thereof. The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００９０】製造法20 化合物（Ｉ−31）またはその塩は、化合物（Ｉ−９）ま
たはその塩をハロゲン化に付すことにより製造できる。
このハロゲン化は、通常、慣用のハロゲン化剤、たとえ
ばハロゲン（たとえば塩素、臭素など）、三ハロゲン化
燐（たとえば三臭化燐、三塩化燐など）、五ハロゲン化
燐（たとえば五塩化燐、五臭化燐など）、オキシ塩化燐
（たとえば三塩化ホスホリル、一塩化ホスホリルな
ど）、ハロゲン化チオニル（たとえば塩化チオニル、臭
化チオニルなど）、ハロゲン化オキザリル（たとえば塩
化オキザリル、臭化オキザリルなど）、ハロゲン化スル
フリル（たとえば塩化スルフリルなど）、ピリジン臭化
水素酸塩過臭化物などを用いて実施する。Production Method 20 Compound (I-31) or a salt thereof can be produced by subjecting compound (I-9) or a salt thereof to halogenation.
This halogenation is usually carried out using a conventional halogenating agent such as halogen (eg, chlorine, bromine, etc.), phosphorus trihalide (eg, phosphorus tribromide, phosphorus trichloride, etc.), phosphorus pentahalide (eg, phosphorus pentachloride, Phosphorus pentabromide, etc., phosphorus oxychloride (eg, phosphoryl trichloride, phosphoryl monochloride, etc.), thionyl halide (eg, thionyl chloride, thionyl bromide, etc.), oxalyl halide (eg, oxalyl chloride, oxalyl bromide, etc.), It is carried out using sulfuryl halide (eg, sulfuryl chloride), pyridine hydrobromide perbromide, and the like.
【００９１】この反応は、通常、水、アルコール（たと
えばメタノール、エタノール、イソプロピルアルコール
など）、ベンゼン、ジオキサン、Ｎ,Ｎ−ジメチルホル
ムアミド、テトラヒドロフラン、塩化メチレン、二塩化
エチレン、クロロホルム、ジエチルエーテルなどの溶媒
または反応に悪影響を及ぼさないその他の任意の溶媒中
で実施する。反応温度はとくに限定されないが、通常
は、冷却下ないし加温下で反応を実施する。This reaction is usually carried out in a solvent such as water, alcohol (eg, methanol, ethanol, isopropyl alcohol, etc.), benzene, dioxane, N, N-dimethylformamide, tetrahydrofuran, methylene chloride, ethylene dichloride, chloroform, diethyl ether, etc. Alternatively, the reaction is performed in any other solvent that does not adversely affect the reaction. The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００９２】製造法21 化合物（Ｉ−32）またはその塩は、化合物（Ｉ−９）ま
たはその塩をニトロ化剤と反応させることにより製造で
きる。好適なニトロ化剤は、硝酸、発煙硝酸、硝酸カリ
ウム、テトラフルオロ硼酸ニトロニウムなどである。反
応は、通常、硫酸、酢酸、無水酢酸などの酸または酸無
水物中で実施する。反応温度はとくに限定されず、通
常、冷却下ないし加熱下で反応を実施する。Production Method 21 Compound (I-32) or a salt thereof can be produced by reacting compound (I-9) or a salt thereof with a nitrating agent. Suitable nitrating agents are nitric acid, fuming nitric acid, potassium nitrate, nitronium tetrafluoroborate and the like. The reaction is usually carried out in an acid such as sulfuric acid, acetic acid, acetic anhydride or an acid anhydride. The reaction temperature is not particularly limited, and the reaction is usually carried out under cooling or heating.
【００９３】製造法22 化合物（Ｉ−33）またはその塩は、化合物（Ｉ−７）ま
たはその塩を還元に付すことにより製造できる。この還
元は、ケトンを第二級アルコールに還元しうる有機化学
の分野で常用される一般的方法に従って実施でき、好適
な還元剤は、たとえば、アルミニウム水素化物（たとえ
ば水素化アルミニウムリチウム、水素化ジ（低級）アル
キルアルミニウムリチウム、Red−Al（登録商標）な
ど）、硼素水素化物（たとえば水素化硼素ナトリウム、
水素化シアノ硼素ナトリウムなど）などの金属水素化物
である。Production Method 22 Compound (I-33) or a salt thereof can be produced by subjecting compound (I-7) or a salt thereof to reduction. This reduction can be carried out according to common methods commonly used in the field of organic chemistry that can reduce ketones to secondary alcohols, and suitable reducing agents include, for example, aluminum hydride (eg, lithium aluminum hydride, dihydrogen hydride). (Lower) alkyl aluminum lithium, Red-Al®, etc.), boron hydrides (eg sodium borohydride,
Metal hydride such as sodium cyanoborohydride).
【００９４】反応は、通常、慣用の溶媒、たとえば水、
テトラヒドロフラン、ジオキサン、トルエン、塩化メチ
レン、クロロホルム、Ｎ,Ｎ−ジメチルホルムアミド、
アセトン、反応に悪影響を及ぼさないその他の任意の有
機溶媒またはこれらの混合物中で実施する。反応温度は
とくに限定されないが、通常は、冷却下ないし加温下で
反応を実施する。The reaction is usually carried out using a conventional solvent, for example, water,
Tetrahydrofuran, dioxane, toluene, methylene chloride, chloroform, N, N-dimethylformamide,
The reaction is performed in acetone, any other organic solvent that does not adversely influence the reaction, or a mixture thereof. The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling or heating.
【００９５】製造法23 化合物（Ｉ−35）またはその塩は、化合物（Ｉ−34）ま
たはその塩をヒドロキシルアミンまたはその塩と反応さ
せることにより製造できる。反応は、通常、慣用の溶
媒、たとえば水、アルコール［たとえばメタノール、エ
タノールなど］、アセトン、ジオキサン、アセトニトリ
ル、クロロホルム、塩化メチレン、塩化エチレン、テト
ラヒドロフラン、酢酸エチル、Ｎ,Ｎ−ジメチルホルム
アミド、ジオキサン、反応に悪影響を及ぼさないその他
の任意の有機溶媒中で実施する。これらの慣用の溶媒
は、水との混合物の形で使用することもできる。Production Method 23 Compound (I-35) or a salt thereof can be produced by reacting compound (I-34) or a salt thereof with hydroxylamine or a salt thereof. The reaction is usually carried out using a conventional solvent such as water, alcohol [eg, methanol, ethanol, etc.], acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N, N-dimethylformamide, dioxane, The reaction is performed in any other organic solvent that does not adversely affect the reaction. These conventional solvents can also be used in the form of a mixture with water.
【００９６】反応は、製造法１のところで例示した無機
塩基または有機塩基の存在下で実施するのが好ましい。
反応温度はとくに限定されず、通常、冷却下ないし加熱
下で反応を実施する。The reaction is preferably carried out in the presence of an inorganic base or an organic base exemplified in Production Method 1.
The reaction temperature is not particularly limited, and the reaction is usually carried out under cooling or heating.
【００９７】製造法24 化合物（Ｉ−37）またはその塩は、化合物（Ｉ−36）ま
たはそのアミノ基における反応性誘導体もしくはそれら
の塩を化合物（VI）または化合物（VII）と反応させる
ことにより製造できる。この反応は製造法16と同様にし
て実施でき、従って、使用すべき試薬および反応条件
（たとえば反応温度など）としては、製造法16のそれら
を挙げることができる。本発明では、式（Ｉ）の化合物
のほかに、種々の先行刊行物に開示されている多くのサ
イクリックヌクレオチドPDE阻害作用をもつ化合物を使
用することができる。Production method 24 Compound (I-37) or a salt thereof is prepared by reacting compound (I-36) or a reactive derivative at the amino group thereof or a salt thereof with compound (VI) or compound (VII). Can be manufactured. This reaction can be carried out in the same manner as in Production Method 16. Accordingly, the reagents to be used and the reaction conditions (for example, reaction temperature and the like) include those in Production Method 16. In the present invention, in addition to the compound of the formula (I), many compounds having a cyclic nucleotide PDE inhibitory activity disclosed in various prior publications can be used.
【００９８】とくに、国際特許公開WO 93／07124および
欧州特許公開0526004に開示されているサイクリックヌ
クレオチドPDE（とくにcGMP−PDE）阻害活性を有する式In particular, the compounds having cyclic nucleotide PDE (especially cGMP-PDE) inhibitory activity disclosed in International Patent Publication WO 93/07124 and European Patent Publication 0526004
【化３５】の化合物、およびその類縁化合物、ならびに式Embedded image A compound of the formula:
【化３６】の化合物およびその類縁化合物が本発明で使用できる。
そして、バイオケミカル・ファーマコロジー（Biochem.
Pharmacol.）46巻５号833〜839頁などに開示されてい
る種々のサイクリックヌクレオチドPDE阻害剤（たとえ
ばパパベリン、ジピリダモールなど）も、本発明で用い
ることができる。また、現在までに、上に例示したcGMP
−PDE阻害剤は、種々の疾患、たとえば、国際公開WO 93
／07124によれば、狭心症、心筋梗塞、慢性および急性
心不全全などの虚血性心疾患、肺性心を併発していても
よい肺高血圧、種々の因子に起因する高血圧、末梢循環
不全、脳機能障害、気管支炎性喘息、および、たとえば
アトピー性皮膚炎、アレルギー性鼻炎などのアレルギー
疾患の治療または予防に有用であることも知られてい
る。Embedded image And analogs thereof can be used in the present invention.
And, Biochemical Pharmacology (Biochem.
Pharmacol., Vol. 46, No. 5, pp. 833-839 and the like (for example, papaverine, dipyridamole, etc.) can also be used in the present invention. Also, to date, the cGMP exemplified above
-PDE inhibitors can be used for various diseases, such as WO 93
According to / 07124, angina pectoris, myocardial infarction, ischemic heart disease such as chronic and acute heart failure, pulmonary hypertension optionally combined with pulmonary heart, hypertension due to various factors, peripheral circulatory insufficiency, It is also known to be useful for treating or preventing cerebral dysfunction, bronchitis asthma, and allergic diseases such as, for example, atopic dermatitis, allergic rhinitis.
【００９９】SLEは出産年齢にある女性が主に罹患する
自己免疫疾患であり、T-リンパ球の過増殖、核抗原特に
二重鎖-DNAに対する自己抗体の発生、免疫複合体が関与
する病理によって特徴づけられる[R. Berlett, Scand.
J. Rheum., 75 290 (1988 Supp.)]。血中免疫複合体
は、多くのSLEの臨床症状の直接的原因となっている。S
LEの臨床症状は、ほとんどすべての組織に観察され、限
定はされないが次のものを含む：全身症状--疲労、倦
怠、発熱、食欲不振、悪心、体重減少等；筋・骨格症状
--関節痛/筋肉痛、虚血性骨壊死等；皮膚症状--頬部皮
疹、口腔内潰瘍、その他の皮疹、脱毛症、脈管炎等；血
液学的症状--貧血、白血球減少、脾腫、リンパ節腫脹
等；神経症状--痙攣、末梢神経障害等；循環呼吸器症状
--胸膜炎、心筋炎、狼蒼性肺炎等；腎症状--蛋白尿、ネ
フローゼ症候群（例えば、ループス腎炎）、腎不全等；
消化器症状--腹水、肝酵素異常等；血栓症；胎児死亡；
眼症状--網膜脈管炎、結膜炎/上強皮炎等（ハリソン内
科書(第１２版)、吉利 和他 監訳 p2569-2579 1996
年、廣川書店）。SLE is an autoimmune disease that mainly affects women of childbearing age, including hyperproliferation of T-lymphocytes, generation of autoantibodies against nuclear antigens, particularly double-stranded DNA, and pathology involving immune complexes. [R. Berlett, Scand.
J. Rheum., 75 290 (1988 Supp.)]. Blood immune complexes are a direct cause of many SLE clinical manifestations. S
Clinical symptoms of LE are observed in almost all tissues and include, but are not limited to: systemic symptoms-fatigue, malaise, fever, anorexia, nausea, weight loss, etc .;
-Arthralgia / muscle pain, ischemic osteonecrosis, etc .; cutaneous symptoms-buccal rash, oral ulcers, other rashes, alopecia, vasculitis, etc .; hematological symptoms-anemia, leukopenia, splenomegaly Nervous symptoms--convulsions, peripheral neuropathy, etc .; cardiorespiratory symptoms
-Pleurisy, myocarditis, lupus pneumonia, etc .; renal symptoms-proteinuria, nephrotic syndrome (eg, lupus nephritis), renal failure, etc .;
Gastrointestinal symptoms-ascites, liver enzyme abnormalities, etc .; thrombosis; fetal death;
Ocular symptoms-retinal vasculitis, conjunctivitis / scleroderma, etc. (Harrison Internal Medicine (Twelfth Edition), Kazuyoshi Giri et al.
Year, Hirokawa Shoten).
【０１００】更にループス腎炎はびまん性ループス腎
炎、巣状分節状ループス腎炎、膜性ループス腎炎、メサ
ンギウム性ループス腎炎に分類される。サイクリックヌ
クレオチドPDEとしては、サイクリックアデノシン３’,
５’−一燐酸ホスホジエステラーゼ（以下cAMP−PDEと
呼ぶ）およびcGMP−PDEが挙げられる。cAMP−PDEおよび
cGMP−PDEは、それぞれcAMPおよびcGMPの細胞内濃度の
調節において主要な役割を演じている。サイクリックヌ
クレオチドPDEは、主として一次蛋白質およびcDNA配列
の情報に基いて、次の５つのアイソザイム族に分類され
る：Ca++−カルモジュリン（CaM）依存性のもの（Ｉ
型）；cGMPにより刺激されるもの（II型）；ミルリノン
などの多くの変力動作用陽性物質により、cGMPにより阻
害されるもの（III型）；ロリプラム（relipram）によ
り選択的に阻害されるcAMP特異性のもの（IV型）；ザプ
リナスト（Zaprinast）により選択的に阻害されるcGMP
特異性のもの（Ｖ型）。Further, lupus nephritis is classified into diffuse lupus nephritis, focal segmental lupus nephritis, membranous lupus nephritis, and mesangial lupus nephritis. As cyclic nucleotide PDE, cyclic adenosine 3 ',
5'-monophosphate phosphodiesterase (hereinafter referred to as cAMP-PDE) and cGMP-PDE. cAMP-PDE and
cGMP-PDE plays a major role in regulating intracellular concentrations of cAMP and cGMP, respectively. Cyclic nucleotides PDEs are classified into the following five isozyme families, mainly based on information on primary protein and cDNA sequences: Ca++ -calmodulin (CaM) dependent (I
Those stimulated by cGMP (type II); those inhibited by cGMP by many inotropic positive substances such as milrinone (type III); cAMP selectively inhibited by rolipram (relipram) Specificity (type IV); cGMP selectively inhibited by zaprinast
Specific (type V).
【０１０１】本発明の医薬製剤は、有効成分としてサイ
クリックヌクレオチドPDE阻害剤を純粋なまたは不純物
を含む形で、単一化合物または混合物として、外用、経
腸、静脈内、筋肉内または非経口適用に適した有機また
は無機担体または賦形剤との混合物として含有する、た
とえば固体、半固体または液体形態のものである。有効
成分は、たとえば、軟膏剤、クリーム剤、硬膏剤、錠
剤、ペレット剤、カプセル剤、坐剤、液剤（たとえば食
塩液）、乳剤、懸濁剤（たとえばオリーブ油）、その他
の使用に適した任意の形態用の製薬上許容しうる常用の
無毒性担体と配合できる。使用できる担体は、水、ワッ
クス、グルコース、ラクトース、アラビアゴム、ゼラチ
ン、マンニトール、でんぷんペースト、三珪酸マグネシ
ウム、タルク、コーンスターチ、ケラチン、パラフィ
ン、コロイドシリカ、じゃがいもでんぷん、尿素、製剤
の製造に用いるのに適したその他の固体状、半固体状ま
たは液状の担体であり、さらに、補助物質、佐剤、安定
剤、増粘剤、着色剤、香料を用いてもよい。活性化合物
は、疾患の過程または病状に対して所望の効果を奏する
のに十分な有効量を医薬製剤に含有させることができ
る。The pharmaceutical preparation of the present invention can be used as a single compound or a mixture containing a cyclic nucleotide PDE inhibitor as an active ingredient, pure or containing impurities, for external, enteral, intravenous, intramuscular, or parenteral application. For example, in solid, semi-solid or liquid form, as a mixture with an organic or inorganic carrier or excipient suitable for the present invention. Active ingredients include, for example, ointments, creams, plasters, tablets, pellets, capsules, suppositories, solutions (eg, saline), emulsions, suspensions (eg, olive oil), and any other suitable for use. And pharmaceutically acceptable conventional non-toxic carriers. Carriers that can be used include water, wax, glucose, lactose, gum arabic, gelatin, mannitol, starch paste, magnesium trisilicate, talc, corn starch, keratin, paraffin, colloidal silica, potato starch, urea, and for use in the manufacture of preparations. Other suitable solid, semi-solid or liquid carriers are also suitable, as well as auxiliary substances, adjuvants, stabilizers, thickeners, coloring agents and perfumes. The active compound can be included in the pharmaceutical formulation in an effective amount sufficient to produce the desired effect on the course or condition of the disease.
【０１０２】本発明により処置できる哺乳動物として
は、ウシ、ウマなどの牧畜哺乳動物、イヌ、ネコ、ラッ
トなどの家畜およびヒトが挙げられ、好ましいのはヒト
である。この組成物をヒトに適用するには、外用（局
所）、経口、非経口、経腸、静脈内または筋肉内投与に
より適用するのが好ましい。The mammals that can be treated according to the present invention include domesticated mammals such as cows and horses, domestic animals such as dogs, cats and rats, and humans, and humans are preferred. For applying this composition to humans, it is preferable to apply it by external (topical), oral, parenteral, enteral, intravenous or intramuscular administration.
【０１０３】活性化合物の治療有効用量は、処置すべき
各個の患者の年令および病状により変化し、それらに依
存もするが、全身的適用の場合には、１日量約0.01〜10
00mg、好ましくは0.1〜500mg、より好ましくは0.5〜100
mgの有効成分を疾患処置のために投与するのが一般的で
あり、一般には、平均１回量約0.2〜0.5mg、１mg、５m
g、10mg、50mg、100mg、250mgおよび500mgを投与する。
ヒトでの長期投与のための１日量は、約0.3mg−1000mg
／kg／日の範囲内にあるであろう。The therapeutically effective dose of active compound will vary with and depends on the age and condition of the individual patient to be treated, but for systemic applications a daily dose of about 0.01-10.
00 mg, preferably 0.1-500 mg, more preferably 0.5-100
It is common to administer 1 mg of the active ingredient for the treatment of disease, generally with an average dose of about 0.2-0.5 mg, 1 mg, 5 mg
g, 10 mg, 50 mg, 100 mg, 250 mg and 500 mg are administered.
The daily dose for long-term administration in humans is about 0.3mg-1000mg
/ Kg / day.
【０１０４】[0104]
【発明の効果】この発明の発明者は、驚くべきことに、
サイクリックヌクレオチドPDE阻害剤を有効成分として
含む医薬製剤がＬＥ、特にＳＬＥ、とりわけループス腎
炎の治療または予防に有用であることを見出した。本発
明の有用性を示すために、サイクリックヌクレオチドPD
E阻害剤として化合物（Ｉ）を選び、それを含有する製
剤の代表的化合物の活性を以下に示す。The inventor of the present invention surprisingly found that
It has been found that a pharmaceutical preparation containing a cyclic nucleotide PDE inhibitor as an active ingredient is useful for treating or preventing LE, especially SLE, especially lupus nephritis. To demonstrate the utility of the present invention, the cyclic nucleotide PD
Compound (I) was selected as an E inhibitor, and the activity of a representative compound in a preparation containing the compound is shown below.
【０１０５】試験１ NZB x NZW/F1マウスでの免疫複合体腎炎に対する試験化
合物の効果 雌NZB x NZW/F1マウスを標準的な温度、日照、給水条件
でケージあたり４匹づつ飼育した。動物に19.6%カゼイ
ン、57.3%デキストラン、18%脂肪、3.5%調整塩を及び必
須ビタミンを含む高カロリー飼料を与えた。２７月齢の
初めに1mg/kg 又は10mg/kgの試験化合物を体重1kgあた
り10mlとなるように毎日2回投与した。４２月齢にマウ
スを屠殺し、血清及び尿の分析を行った。本発明の代表
的化合物として選ばれた製造例80-(8)で製造された試験
化合物を含有する製剤は、BUN、蛋白尿、クレアチンク
リアランスなどの血清及び尿中のパラメータを改善し、
二重鎖DNAへの自己抗体の血中レベルを低下させた。Test 1 Effect of Test Compound on Immune Complex Nephritis in NZB x NZW / F1 Mice Female NZB x NZW / F1 mice were housed 4 per cage under standard temperature, sunshine and water supply conditions. Animals were fed a high calorie diet containing 19.6% casein, 57.3% dextran, 18% fat, 3.5% adjusted salt and essential vitamins. At the beginning of the 27 months of age, 1 mg / kg or 10 mg / kg of the test compound was administered twice daily at 10 ml / kg body weight. Mice were sacrificed at 42 months of age and analyzed for serum and urine. Preparation containing the test compound prepared in Production Example 80- (8) selected as a representative compound of the present invention improves serum and urine parameters such as BUN, proteinuria, and creatine clearance,
Blood levels of autoantibodies to double-stranded DNA were reduced.
【０１０６】試験２ 化合物（Ｉ）の毒性 この発明の代表的化合物として選択した製造例59および
80−(8)で製造した化合物の反復経口投与による毒性試
験をSDラットで実施した。用量32mg／kg、１日１回連続
14日間投与で、死亡は観察できなかった。なお、欧州特
許公開579496、534443、526004、636626；米国特許3819
631、5294612、5488055；国際特許出願93／07124、94／
19351；日本国特許出願公開平７−330777；などに記載
されている、サイクリックヌクレオチドPDE阻害活性を
有する化合物は、ＬＥ、特にＳＬＥ、とりわけループス
腎炎の治療または予防に有用であると考えられる。Test 2 Toxicity of Compound (I) Production Example 59 selected as a representative compound of the present invention and
A toxicity test by repeated oral administration of the compound prepared in 80- (8) was performed on SD rats. 32mg / kg once daily
No mortality was observed after 14 days of administration. In addition, European Patent Publication 579496, 534443, 526004, 636626; US Patent 3819
631,5294612,5488055; International Patent Applications 93 / 07124,94 /
Compounds having a cyclic nucleotide PDE inhibitory activity described in, for example, JP 19351; Japanese Patent Application Publication No. Hei 7-330777; are considered to be useful for the treatment or prevention of LE, especially SLE, especially lupus nephritis.
【０１０７】本発明で使用する化合物（Ｉ）は、以下の
製造例により製造できる。 製造例１ (1) トリフルオロメタンスルホン酸２−アミノ−４−メ
トキシカルボニルフェニルエステル（2.6ｇ）のピリジ
ン（5.6ml）−ジクロロメタン（20ml）混合物溶液に、
０℃で、クロロ蟻酸ベンジル（2.08ml）を加え、混合物
を20℃で4.5時間撹拌した。混合物をジクロロメタンで
希釈し、希塩酸、重炭酸ナトリウム水溶液および食塩水
で順次洗った。有機層を硫酸ナトリウムで乾燥し、真空
下で蒸発させた。残留物をシリカゲルクロマトグラフィ
ーに付し、ジクロロメタンで溶出して、トリフルオロメ
タンスルホン酸２−ベンジルオキシカルボニルアミノ−
４−メトキシカルボニルフェニルエステル（2.61ｇ）を
無色結晶として得た。 NMR (CDCl3,δ) : 3.92 (3H,s), 5.23 (2H,s), 6.89 (1
H,br s), 7.3-7.45(6H,m), 7.83 (1H,dd,J=1, 8Hz), 8.
81 (1H,s) (2) トリフルオロメタンスルホン酸２−ベンジルオキシ
カルボニルアミノ−４−メトキシカルボニルフェニルエ
ステル（1.01ｇ）、１−ペンチニル（トリブチル）スタ
ンナン（1.02ｇ）、塩化リチウム（0.29ｇ）およびテト
ラキス（トリフェニルホスフィン）パラジウム（80mg）
のジオキサン（24ml）中混合物を、100℃で２時間加熱
した。真空下で溶媒を蒸発させ、残留物をシリカゲルク
ロマトグラフィーに付し、ヘキサン−酢酸エチル（４：
１）混合物で溶出して、３−ベンジルオキシカルボニル
アミノ−４−（１−ペンチニル）安息香酸メチルエステ
ル（536mg）を無色結晶として得た。 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.67 (2H,m),
2.44 (2H,t,J=7Hz),3.87 (3H,s), 5.23 (2H,s), 7.25-
7.7 (7H,m), 8.78 (1H,s)The compound (I) used in the present invention can be produced according to the following production examples. Production Example 1 (1) To a solution of trifluoromethanesulfonic acid 2-amino-4-methoxycarbonylphenyl ester (2.6 g) in a mixture of pyridine (5.6 ml) and dichloromethane (20 ml) was added.
At 0 ° C., benzyl chloroformate (2.08 ml) was added and the mixture was stirred at 20 ° C. for 4.5 hours. The mixture was diluted with dichloromethane and washed sequentially with dilute hydrochloric acid, aqueous sodium bicarbonate and brine. The organic layer was dried over sodium sulfate and evaporated under vacuum. The residue was chromatographed on silica gel eluting with dichloromethane to give 2-benzyloxycarbonylamino-trifluoromethanesulfonate.
4-methoxycarbonylphenyl ester (2.61 g) was obtained as colorless crystals. NMR (CDCl3 , δ): 3.92 (3H, s), 5.23 (2H, s), 6.89 (1
H, brs), 7.3-7.45 (6H, m), 7.83 (1H, dd, J = 1,8Hz), 8.
81 (1H, s) (2) 2-benzyloxycarbonylamino-4-methoxycarbonylphenyl trifluoromethanesulfonate (1.01 g), 1-pentynyl (tributyl) stannane (1.02 g), lithium chloride (0.29 g) and Tetrakis (triphenylphosphine) palladium (80mg)
Of dioxane (24 ml) was heated at 100 ° C. for 2 hours. The solvent was evaporated under vacuum and the residue was chromatographed on silica gel with hexane-ethyl acetate (4: 4).
1) Elution with the mixture gave methyl 3-benzyloxycarbonylamino-4- (1-pentynyl) benzoate (536 mg) as colorless crystals. NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.67 (2H, m),
2.44 (2H, t, J = 7Hz), 3.87 (3H, s), 5.23 (2H, s), 7.25-
7.7 (7H, m), 8.78 (1H, s)
【０１０８】(3) ３−ベンジルオキシカルボニルアミノ
−４−（１−ペンチニル）安息香酸メチルエステル（94
9mg）のテトラヒドロフラン（24ml）溶液に、アルゴン
雰囲気下、塩化金（III）ナトリウム（24mg）を加え、
混合物を還流下に100時間加熱した。真空下で溶媒を蒸
発させ、残留物をシリカゲルクロマトグラフィーに付
し、ヘキサン−ジクロロメタン−酢酸エチル（６：３：
２）混合物で溶出して、１−ベンジルオキシカルボニル
−２−プロピルインドール−６−カルボン酸メチルエス
テル（852mg）を無色結晶として得た。 NMR (CDCl3,δ) : 0.98 (3H,t,J=7Hz), 1.71 (2H,m),
2.97 (2H,t,J=7Hz),3.90 (3H,s), 5.49 (2H,s), 6.39
(1H,s), 7.3-7.6 (6H,m), 7.91 (1H,dd,J=1, 8Hz), 8.8
0 (1H,s) (4) １−ベンジルオキシカルボニル−２−プロピルイン
ドール−６−カルボン酸メチルエステル（200mg）のメ
タノール−酢酸エチル混合物（１：１、８ml）溶液に、
10％パラジウム炭素（30mg）を加え、混合物を水素雰囲
気下で20分間撹拌した。セライトを通して触媒を濾去
し、メタノールで洗った。濾液を真空下で蒸発させて、
２−プロピルインドール−６−カルボン酸メチルエステ
ル（112mg）を無色結晶として得た。 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.78 (2H,m),
2.76 (2H,t,J=7Hz),3.93 (3H,s), 6.29 (1H,s), 7.51
(1H,d,J=8Hz), 7.77 (1H,d,J=8Hz),8.04 (1H,s), 8.15
(1H,br s)(3) 3-benzyloxycarbonylamino-4- (1-pentynyl) benzoic acid methyl ester (94
To a solution of 9 mg) in tetrahydrofuran (24 ml) was added sodium gold (III) chloride (24 mg) under an argon atmosphere.
The mixture was heated under reflux for 100 hours. The solvent was evaporated under vacuum and the residue was chromatographed on silica gel with hexane-dichloromethane-ethyl acetate (6: 3:
2) Elution with the mixture gave 1-benzyloxycarbonyl-2-propylindole-6-carboxylic acid methyl ester (852 mg) as colorless crystals. NMR (CDCl3 , δ): 0.98 (3H, t, J = 7Hz), 1.71 (2H, m),
2.97 (2H, t, J = 7Hz), 3.90 (3H, s), 5.49 (2H, s), 6.39
(1H, s), 7.3-7.6 (6H, m), 7.91 (1H, dd, J = 1, 8Hz), 8.8
0 (1H, s) (4) A solution of 1-benzyloxycarbonyl-2-propylindole-6-carboxylic acid methyl ester (200 mg) in a methanol-ethyl acetate mixture (1: 1, 8 ml) was added to
10% Palladium on carbon (30 mg) was added and the mixture was stirred under a hydrogen atmosphere for 20 minutes. The catalyst was filtered off through celite and washed with methanol. The filtrate was evaporated under vacuum,
2-propylindole-6-carboxylic acid methyl ester (112 mg) was obtained as colorless crystals. NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.78 (2H, m),
2.76 (2H, t, J = 7Hz), 3.93 (3H, s), 6.29 (1H, s), 7.51
(1H, d, J = 8Hz), 7.77 (1H, d, J = 8Hz), 8.04 (1H, s), 8.15
(1H, br s)
【０１０９】(5) 塩化アルミニウム（294mg）と塩化ア
セチル（0.08ml）とのジクロロメタン（10ml）懸濁液
に、２−プロピルインドール−６−カルボン酸メチルエ
ステル（200mg）を加え、混合物を20℃で１時間撹拌し
た。生じた混合物を氷上に注ぎ、酢酸エチルで抽出し
た。合せた有機層を、重炭酸ナトリウム水溶液および食
塩水で洗い、つぎに硫酸ナトリウムで乾燥し、真空下で
蒸発させた。残留物をイソプロピルエーテルを用いて粉
末化させて、３−アセチル−２−プロピルインドール−
６−カルボン酸メチルエステル（78mg）を無色結晶とし
て得た。 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.81 (2H,m),
2.69 (3H,s), 3.18(2H,t,J=7Hz), 3.96 (3H,s), 7.93
(1H,dd,J=1, 8Hz), 8.01 (1H,d,J=8Hz), 8.12 (1H,d,J=
1Hz), 8.88 (1H,br s)(5) To a suspension of aluminum chloride (294 mg) and acetyl chloride (0.08 ml) in dichloromethane (10 ml) was added 2-propylindole-6-carboxylic acid methyl ester (200 mg), and the mixture was added at 20 ° C. For 1 hour. The resulting mixture was poured on ice and extracted with ethyl acetate. The combined organic layers were washed with aqueous sodium bicarbonate and brine, then dried over sodium sulfate and evaporated in vacuo. The residue was triturated with isopropyl ether to give 3-acetyl-2-propylindole-
6-Carboxylic acid methyl ester (78 mg) was obtained as colorless crystals. NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.81 (2H, m),
2.69 (3H, s), 3.18 (2H, t, J = 7Hz), 3.96 (3H, s), 7.93
(1H, dd, J = 1,8Hz), 8.01 (1H, d, J = 8Hz), 8.12 (1H, d, J =
1Hz), 8.88 (1H, br s)
【０１１０】製造例２ ２−プロピルインドール−６−カルボン酸メチルエステ
ル（700mg）と塩化イソブチリル（1.01ml）とから、製
造例１−(5)と同様にして、３−イソブチリル−２−プ
ロピルインドール−６−カルボン酸メチルエステル（47
4mg）を製造した。 NMR (CDCl3,δ) : 1.04 (3H,t,J=8Hz), 1.28 (6H,d,J=8
Hz), 1.83 (2H,sextet,J=8Hz), 3.18 (2H,t,J=8Hz), 3.
52 (2H,septet,J=8Hz), 3.96(3H,s), 7.92 (2H,s), 8.1
6 (1H,s), 9.13 (1H,br s)Production Example 2 3-Isobutyryl-2-propylindole was prepared from 2-propylindole-6-carboxylic acid methyl ester (700 mg) and isobutyryl chloride (1.01 ml) in the same manner as in Production Example 1- (5). -6-carboxylic acid methyl ester (47
4 mg). NMR (CDCl3 , δ): 1.04 (3H, t, J = 8Hz), 1.28 (6H, d, J = 8
Hz), 1.83 (2H, sextet, J = 8Hz), 3.18 (2H, t, J = 8Hz), 3.
52 (2H, septet, J = 8Hz), 3.96 (3H, s), 7.92 (2H, s), 8.1
6 (1H, s), 9.13 (1H, br s)
【０１１１】製造例３ ２−プロピルインドール−６−カルボン酸メチルエステ
ル（500mg）と塩化プロピオニル（0.40ml）とから、製
造例１−(5)と同様にして、３−プロピオニル−２−プ
ロピルインドール−６−カルボン酸メチル（298mg）を
製造した。 NMR (CDCl3,δ) : 1.04 (3H,t,J=8Hz), 1.29 (3H,t,J=8
Hz), 1.83 (2H,sextet,J=8Hz), 3.06 (2H,q,J=8Hz), 3.
20 (2H,t,J=8Hz), 3.96 (3H,s),7.93 (1H,dd,J=1, 8H
z), 8.00 (1H,d,J=8Hz), 8.15 (1H,d,J=1Hz),9.22 (1H,
s)Production Example 3 3-Propionyl-2-propylindole was prepared from 2-propylindole-6-carboxylic acid methyl ester (500 mg) and propionyl chloride (0.40 ml) in the same manner as in Production Example 1- (5). Methyl-6-carboxylate (298 mg) was prepared. NMR (CDCl3 , δ): 1.04 (3H, t, J = 8Hz), 1.29 (3H, t, J = 8
Hz), 1.83 (2H, sextet, J = 8Hz), 3.06 (2H, q, J = 8Hz), 3.
20 (2H, t, J = 8Hz), 3.96 (3H, s), 7.93 (1H, dd, J = 1,8H
z), 8.00 (1H, d, J = 8Hz), 8.15 (1H, d, J = 1Hz), 9.22 (1H,
s)
【０１１２】製造例４ (1) トリフルオロメタンスルホン酸−２−ベンジルオキ
シカルボニルアミノ−４−メトキシカルボニルフェニル
エステル（3.0ｇ）と（４−メチル−１−ペンチニル）
（トリブチル）スタンナン（2.7ｇ）とから、製造例１
−(2)と同様にして、３−ベンジルオキシカルボニルア
ミノ−４−（４−メチル−１−ペンチニル）安息香酸メ
チルエステル（2.25ｇ）を製造した。 NMR (CDCl3,δ) : 1.05 (6H,d,J=8Hz), 1.88-2.02 (1H,
m), 2.40 (2H,d,J=8Hz), 3.90 (3H,s), 5.25 (2H,s),
7.32-7.45 (6H,m), 7.52 (1H,s),7.66 (1H,d,J=8Hz),
8.78 (1H,s) (2) ３−ベンジルオキシカルボニルアミノ−４−（４−
メチル−１−ペンチニル）安息香酸メチルエステル（2.
15ｇ）から、製造例１−(3)と同様にして、１−ベンジ
ルオキシカルボニル−２−イソブチルインドール−６−
カルボン酸メチルエステル（1.67ｇ）を製造した。 NMR (CDCl3,δ) : 0.90 (6H,d,J=8Hz), 1.90-2.04 (1H,
m), 2.86 (2H,d,J=8Hz), 3.90 (3H,s), 5.48 (2H,s),
6.38 (1H,s), 7.40-7.56 (6H,m),7.91 (1H,d,J=8Hz),
8.82 (1H,s)Production Example 4 (1) Trifluoromethanesulfonic acid-2-benzyloxycarbonylamino-4-methoxycarbonylphenyl ester (3.0 g) and (4-methyl-1-pentynyl)
Production Example 1 from (tributyl) stannane (2.7 g)
In the same manner as in-(2), methyl 3-benzyloxycarbonylamino-4- (4-methyl-1-pentynyl) benzoate (2.25 g) was produced. NMR (CDCl3 , δ): 1.05 (6H, d, J = 8Hz), 1.88-2.02 (1H,
m), 2.40 (2H, d, J = 8Hz), 3.90 (3H, s), 5.25 (2H, s),
7.32-7.45 (6H, m), 7.52 (1H, s), 7.66 (1H, d, J = 8Hz),
8.78 (1H, s) (2) 3-benzyloxycarbonylamino-4- (4-
Methyl-1-pentynyl) benzoic acid methyl ester (2.
From 15 g), 1-benzyloxycarbonyl-2-isobutylindole-6- was prepared in the same manner as in Production Example 1- (3).
Carboxylic acid methyl ester (1.67 g) was prepared. NMR (CDCl3 , δ): 0.90 (6H, d, J = 8Hz), 1.90-2.04 (1H,
m), 2.86 (2H, d, J = 8Hz), 3.90 (3H, s), 5.48 (2H, s),
6.38 (1H, s), 7.40-7.56 (6H, m), 7.91 (1H, d, J = 8Hz),
8.82 (1H, s)
【０１１３】(3) １−ベンジルオキシカルボニル−２−
イソブチルインドール−６−カルボン酸メチルエステル
（1.5ｇ）から、製造例１−(4)と同様にして、２−イソ
ブチルインドール−６−カルボン酸メチルエステル（75
2mg）を製造した。 NMR (CDCl3,δ) : 0.98 (6H,d,J=8Hz), 1.95-2.08 (1H,
m), 2.66 (2H,d,J=8Hz), 3.92 (3H,s), 6.28 (1H,s),
7.53 (1H,d,J=8Hz), 7.76 (1H,d,J=8Hz), 8.08 (1H,s),
8.23 (1H,br s) (4) ２−イソブチルインドール−６−カルボン酸メチル
エステル（300mg）と塩化イソブチリル（0.41ml）とか
ら、製造例１−(5)と同様にして、２−イソブチル−３
−イソブチリルインドール−６−カルボン酸メチルエス
テル（246mg）を製造した。 NMR (CDCl3,δ) : 0.98 (6H,d,J=8Hz), 1.27 (1H,d,J=8
Hz), 2.10-2.23 (1H,m), 3.06 (2H,d,J=8Hz), 3.52 (2
H,septet,J=8Hz), 3.96 (3H,s), 7.92(2H,s), 8.16 (1
H,s), 9.02 (1H,s)(3) 1-benzyloxycarbonyl-2-
From isobutylindole-6-carboxylic acid methyl ester (1.5 g), 2-isobutylindole-6-carboxylic acid methyl ester (75 g) was prepared in the same manner as in Production Example 1- (4).
2 mg). NMR (CDCl3 , δ): 0.98 (6H, d, J = 8Hz), 1.95-2.08 (1H,
m), 2.66 (2H, d, J = 8Hz), 3.92 (3H, s), 6.28 (1H, s),
7.53 (1H, d, J = 8Hz), 7.76 (1H, d, J = 8Hz), 8.08 (1H, s),
8.23 (1H, brs) (4) From 2-isobutylindole-6-carboxylic acid methyl ester (300 mg) and isobutyryl chloride (0.41 ml), as in Production Example 1- (5), 2-isobutyl- 3
-Isobutyrylindole-6-carboxylic acid methyl ester (246 mg) was prepared. NMR (CDCl3 , δ): 0.98 (6H, d, J = 8Hz), 1.27 (1H, d, J = 8
Hz), 2.10-2.23 (1H, m), 3.06 (2H, d, J = 8Hz), 3.52 (2
H, septet, J = 8Hz), 3.96 (3H, s), 7.92 (2H, s), 8.16 (1
H, s), 9.02 (1H, s)
【０１１４】製造例５ (1) トリフルオロメタンスルホン酸２−ベンジルオキシ
カルボニルアミノ−４−メトキシカルボニルフェニルエ
ステル（1.82ｇ）と１−ブチニル（トリブチル）スタン
ナン（1.51ｇ）とから、製造例１−(2)と同様にして、
３−ベンジルオキシカルボニルアミノ−４−（１−ブチ
ニル）安息香酸メチルエステル（646mg）を製造した。 NMR (CDCl3,δ) : 1.26 (3H,t,J=7Hz), 2.50 (2H,q,J=7
Hz), 3.91 (3H,s),5.24 (2H,s), 7.3-7.5 (7H,m), 7.65
(1H,dd,J=1, 8Hz), 8.79 (1H,br s) (2) ３−ベンジルオキシカルボニルアミノ−４−（１−
ブチニル）安息香酸メチルエステル（640mg）から、製
造例１−(3)と同様にして、１−ベンジルオキシカルボ
ニル−２−エチルインドール−６−カルボン酸メチルエ
ステル（551mg）を製造した。 NMR (CDCl3,δ) : 1.30 (3H,t,J=7Hz), 3.05 (2H,q,J=7
Hz), 3.88 (3H,s),4.98 (2H,s), 6.92 (1H,s), 7.35-7.
60 (6H,m), 7.89 (1H,dd,J=1,8Hz), 8.79 (1H,s)Production Example 5 (1) Production Example 1- (2-benzyloxycarbonylamino-4-methoxycarbonylphenyl ester (1.82 g) and 1-butynyl (tributyl) stannane (1.51 g) were obtained from trifluoromethanesulfonic acid. As in 2),
3-Benzyloxycarbonylamino-4- (1-butynyl) benzoic acid methyl ester (646 mg) was produced. NMR (CDCl3 , δ): 1.26 (3H, t, J = 7Hz), 2.50 (2H, q, J = 7
Hz), 3.91 (3H, s), 5.24 (2H, s), 7.3-7.5 (7H, m), 7.65
(1H, dd, J = 1,8Hz), 8.79 (1H, brs) (2) 3-benzyloxycarbonylamino-4- (1-
From 1-butynyl) benzoic acid methyl ester (640 mg), 1-benzyloxycarbonyl-2-ethylindole-6-carboxylic acid methyl ester (551 mg) was produced in the same manner as in Production Example 1- (3). NMR (CDCl3 , δ): 1.30 (3H, t, J = 7Hz), 3.05 (2H, q, J = 7
Hz), 3.88 (3H, s), 4.98 (2H, s), 6.92 (1H, s), 7.35-7.
60 (6H, m), 7.89 (1H, dd, J = 1,8Hz), 8.79 (1H, s)
【０１１５】(3) １−ベンジルオキシカルボニル−２−
エチルインドール−６−カルボン酸メチルエステル（54
6mg）から、製造例１−(4)と同様にして、２−エチルイ
ンドール−６−カルボン酸メチルエステル（306mg）を
製造した。 NMR (CDCl3,δ) : 1.38 (3H,t,J=7Hz), 2.82 (2H,q,J=7
Hz), 3.91 (3H,s),6.30 (1H,s), 7.50 (1H,d,J=8Hz),
7.75 (1H,d,J=8Hz), 8.03 (1H,s),8.14 (1H,br s)(4)
２−エチルインドール−６−カルボン酸メチルエステル
（660mg）と塩化プロピオニル（0.62ml）とから、製造
例１−(5)と同様にして、２−エチル−３−プロピオニ
ルインドール−６−カルボン酸メチルエステル(435mg)
を製造した。 NMR (CDCl3,δ) : 1.29 (3H,t,J=7Hz), 1.39 (3H,t,J=7
Hz), 3.06 (2H,t,J=7Hz), 3.26 (2H,t,J=7Hz), 3.94 (3
H,s), 7.24 (1H,s), 7.92 (1H,d,J=8Hz), 7.98 (1H,d,J
=8Hz), 8.14 (1H,s), 8.92 (1H,br s)(3) 1-benzyloxycarbonyl-2-
Ethylindole-6-carboxylic acid methyl ester (54
6 mg) to produce 2-ethylindole-6-carboxylic acid methyl ester (306 mg) in the same manner as in Production Example 1- (4). NMR (CDCl3 , δ): 1.38 (3H, t, J = 7Hz), 2.82 (2H, q, J = 7
Hz), 3.91 (3H, s), 6.30 (1H, s), 7.50 (1H, d, J = 8Hz),
7.75 (1H, d, J = 8Hz), 8.03 (1H, s), 8.14 (1H, br s) (4)
Methyl 2-ethyl-3-propionylindole-6-carboxylate was prepared from 2-ethylindole-6-carboxylic acid methyl ester (660 mg) and propionyl chloride (0.62 ml) in the same manner as in Production Example 1- (5). Ester (435mg)
Was manufactured. NMR (CDCl3 , δ): 1.29 (3H, t, J = 7Hz), 1.39 (3H, t, J = 7
Hz), 3.06 (2H, t, J = 7Hz), 3.26 (2H, t, J = 7Hz), 3.94 (3
H, s), 7.24 (1H, s), 7.92 (1H, d, J = 8Hz), 7.98 (1H, d, J
= 8Hz), 8.14 (1H, s), 8.92 (1H, br s)
【０１１６】製造例６ (1) インドール−６−カルボン酸メチルエステル（500m
g）と塩化イソブチリル（0.84ml）とから、製造例１−
(5)と同様にして、３−イソブチリルインドール−６−
カルボン酸メチルエステル（618mg）を製造した。 NMR (CDCl3,δ) : 1.28 (6H,d,J=7Hz), 3.35 (1H,m),
3.96 (3H,s), 7.93-8.06 (2H,m), 8.19 (1H,s), 8.46
(1H,d,J=8Hz), 8.96 (1H,br s) (2) ３−イソブチリルインドール−６−カルボン酸メチ
ルエステル（146mg）のテトラヒドロフラン（５ml）溶
液に、ボラン−テトラヒドロフラン錯体の１Ｍテトラヒ
ドロフラン溶液（1.8ml）を加え、混合物を50℃で１時
間撹拌した。生じた混合物を減圧下で蒸発させ、残留物
を塩化アンモニウム水溶液で希釈、冷却し、酢酸エチル
で抽出した。有機層を食塩水で洗い、硫酸ナトリウムで
乾燥した。溶媒を蒸発させたのち、残留物をシリカゲル
クロマトグラフィーに付し、ヘキサン−酢酸エチル
（２：１）混合物で溶出して、３−イソブチルインドー
ル−６−カルボン酸メチルエステル（105mg）を無色結
晶として得た。 NMR (CDCl3,δ) : 0.94 (6H,d,J=7Hz), 1.98 (1H,m),
2.62 (2H,d,J=7Hz),3.93 (3H,s), 7.12 (1H,s), 7.61
(1H,d,J=8Hz), 7.78 (1H,d,J=8Hz),8.08 (1H,s), 8.16
(1H,br s)Production Example 6 (1) Indole-6-carboxylic acid methyl ester (500 m
g) and isobutyryl chloride (0.84 ml), Production Example 1-
In the same manner as in (5), 3-isobutyrylindole-6-
Carboxylic acid methyl ester (618 mg) was prepared. NMR (CDCl3 , δ): 1.28 (6H, d, J = 7Hz), 3.35 (1H, m),
3.96 (3H, s), 7.93-8.06 (2H, m), 8.19 (1H, s), 8.46
(1H, d, J = 8Hz), 8.96 (1H, brs) (2) To a solution of 3-isobutyrylindole-6-carboxylic acid methyl ester (146 mg) in tetrahydrofuran (5 ml) was added 1M of borane-tetrahydrofuran complex. A tetrahydrofuran solution (1.8 ml) was added and the mixture was stirred at 50 ° C. for 1 hour. The resulting mixture was evaporated under reduced pressure, the residue was diluted with aqueous ammonium chloride solution, cooled and extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. After evaporation of the solvent, the residue was chromatographed on silica gel, eluting with a hexane-ethyl acetate (2: 1) mixture to give 3-isobutylindole-6-carboxylic acid methyl ester (105 mg) as colorless crystals. Obtained. NMR (CDCl3 , δ): 0.94 (6H, d, J = 7Hz), 1.98 (1H, m),
2.62 (2H, d, J = 7Hz), 3.93 (3H, s), 7.12 (1H, s), 7.61
(1H, d, J = 8Hz), 7.78 (1H, d, J = 8Hz), 8.08 (1H, s), 8.16
(1H, br s)
【０１１７】(3) ３−イソブチルインドール−６−カル
ボン酸メチルエステル（99mg）と塩化アセチル（0.073m
l）とから、製造例１−(5)と同様にして、２−アセチル
−３−イソブチルインドール−６−カルボン酸メチルエ
ステル（43mg）を製造した。 NMR (CDCl3,δ) : 1.01 (6H,d,J=7Hz), 2.02 (1H,m),
2.69 (3H,s), 2.98(2H,d,J=7Hz), 3.96 (3H,s), 7.73
(1H,d,J=8Hz), 7.79 (1H,d,J=8Hz),8.11 (1H,s), 9.09
(1H,br s)(3) 3-isobutylindole-6-carboxylic acid methyl ester (99 mg) and acetyl chloride (0.073 m
l) to give 2-acetyl-3-isobutylindole-6-carboxylic acid methyl ester (43 mg) in the same manner as in Production Example 1- (5). NMR (CDCl3 , δ): 1.01 (6H, d, J = 7Hz), 2.02 (1H, m),
2.69 (3H, s), 2.98 (2H, d, J = 7Hz), 3.96 (3H, s), 7.73
(1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz), 8.11 (1H, s), 9.09
(1H, br s)
【０１１８】製造例７ (1) インドール−６−カルボン酸メチルエステル（655m
g）と塩化アセチル(0.27ml)とから、製造例１−(5)と同
様にして、３−アセチルインドール−６−カルボン酸メ
チルエステル（470mg）を製造した。 NMR (DMSO-d6,δ) : 2.46 (3H,s), 3.88 (3H,s), 7.79
(1H,d,J=8Hz), 8.10(1H,s), 8.24 (1H,d,J=8Hz), 8.52
(1H,s) (2) ３−アセチルインドール−６−カルボン酸メチルエ
ステル（470mg）から、製造例６−(2)と同様にして、３
−エチルインドール−６−カルボン酸メチルエステル
（327mg）を製造した。 NMR (CDCl3,δ) : 1.33 (3H,t,J=7Hz), 2.78 (2H,q,J=7
Hz), 3.93 (3H,s),7.15 (1H,s), 7.63 (1H,d,J=8Hz),
7.79 (1H,d,J=8Hz), 8.12 (1H,s),8.14 (1H,br s)Production Example 7 (1) Indole-6-carboxylic acid methyl ester (655 m
From g) and acetyl chloride (0.27 ml), 3-acetylindole-6-carboxylic acid methyl ester (470 mg) was produced in the same manner as in Production Example 1- (5). NMR (DMSO-d6 , δ): 2.46 (3H, s), 3.88 (3H, s), 7.79
(1H, d, J = 8Hz), 8.10 (1H, s), 8.24 (1H, d, J = 8Hz), 8.52
(1H, s) (2) 3-acetylindole-6-carboxylic acid methyl ester (470 mg) was prepared in the same manner as in Production Example 6- (2).
-Ethylindole-6-carboxylic acid methyl ester (327 mg) was prepared. NMR (CDCl3 , δ): 1.33 (3H, t, J = 7Hz), 2.78 (2H, q, J = 7
Hz), 3.93 (3H, s), 7.15 (1H, s), 7.63 (1H, d, J = 8Hz),
7.79 (1H, d, J = 8Hz), 8.12 (1H, s), 8.14 (1H, br s)
【０１１９】(3) ３−エチルインドール−６−カルボン
酸メチルエステル（184mg）と塩化プロピオニル（0.17m
l）とから、製造例１−(5)と同様にして、３−エチル−
２−プロピオニルインドール−６−カルボン酸メチルエ
ステル（65.7mg）を製造した。 NMR (CDCl3,δ) : 1.29 (3H,t,J=7Hz), 1.34 (3H,t,J=7
Hz), 3.03 (2H,q,J=7Hz), 3.14 (2H,q,J=7Hz), 3.94 (3
H,s), 7.73 (1H,d,J=8Hz), 7.79(1H,d,J=8Hz), 8.13 (1
H,s), 9.10 (1H,br s)(3) 3-ethylindole-6-carboxylic acid methyl ester (184 mg) and propionyl chloride (0.17 m
l), 3-ethyl- was obtained in the same manner as in Production Example 1- (5).
2-Propionyl indole-6-carboxylic acid methyl ester (65.7 mg) was prepared. NMR (CDCl3 , δ): 1.29 (3H, t, J = 7Hz), 1.34 (3H, t, J = 7
Hz), 3.03 (2H, q, J = 7Hz), 3.14 (2H, q, J = 7Hz), 3.94 (3
H, s), 7.73 (1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz), 8.13 (1
H, s), 9.10 (1H, br s)
【０１２０】製造例８ (1) ３−イソブチリル−２−プロピルインドール−６−
カルボン酸メチルエステル（935mg）から、実施例２と
同様にして、３−イソブチリル−２−プロピルインドー
ル−６−カルボン酸（853mg）を製造した。 NMR (DMSO-d6,δ) : 0.95 (3H,t,J=8Hz), 1.14 (6H,d,J
=8Hz), 1.72 (2H,sextet,J=8Hz), 3.08 (2H,t,J=8Hz),
3.46 (1H,septet,J=8Hz), 7.76(1H,d,J=9Hz), 7.92 (1
H,dd,J=1, 9Hz), 8.00 (1H,d,J=1Hz) (2) ３−イソブチリル−２−プロピルインドール−６−
カルボン酸（935mg）から、実施例６と同様にして、３
−イソブチリル−２−プロピルインドール−６−カルボ
キサアミド（853mg）を製造した。 NMR (DMSO-d6,δ) : 0.95 (3H,t,J=8Hz), 1.15 (6H,d,J
=8Hz), 1.70 (2H,sextet,J=8Hz), 3.07 (2H,t,J=8Hz),
3.46 (1H,septet,J=8Hz), 7.26(1H,br s), 7.72 (1H,d,
J=9Hz), 7.87 (1H,dd,J=1, 9Hz), 7.94 (1H,d,J=1Hz)Production Example 8 (1) 3-Isobutyryl-2-propylindole-6
In a manner similar to Example 2, 3-isobutyryl-2-propylindole-6-carboxylic acid (853 mg) was produced from carboxylic acid methyl ester (935 mg). NMR (DMSO-d6 , δ): 0.95 (3H, t, J = 8Hz), 1.14 (6H, d, J
= 8Hz), 1.72 (2H, sextet, J = 8Hz), 3.08 (2H, t, J = 8Hz),
3.46 (1H, septet, J = 8Hz), 7.76 (1H, d, J = 9Hz), 7.92 (1
(H, dd, J = 1,9Hz), 8.00 (1H, d, J = 1Hz) (2) 3-isobutyryl-2-propylindole-6
From carboxylic acid (935 mg), 3
-Isobutyryl-2-propylindole-6-carboxamide (853 mg) was prepared. NMR (DMSO-d6 , δ): 0.95 (3H, t, J = 8Hz), 1.15 (6H, d, J
= 8Hz), 1.70 (2H, sextet, J = 8Hz), 3.07 (2H, t, J = 8Hz),
3.46 (1H, septet, J = 8Hz), 7.26 (1H, br s), 7.72 (1H, d,
J = 9Hz), 7.87 (1H, dd, J = 1, 9Hz), 7.94 (1H, d, J = 1Hz)
【０１２１】製造例９ ２−プロピルインドール−６−カルボン酸メチルエステ
ル（500mg）と塩化ベンゾイル（970mg）とから、製造例
１−(5)と同様にして、３−ベンゾイル−２−プロピル
インドール−６−カルボン酸メチルエステル（289mg）
を製造した。 NMR (CDCl3,δ) : 0.82 (3H,t,J=8Hz), 1.66 (2H,sexte
t,J=8Hz), 2.78 (2H,t,J=8Hz), 3.85 (3H,s), 7.29 (1
H,d,J=8Hz), 7.49-7.54 (2H,m), 7.60-7.64 (4H,m), 8.
02 (1H,s)Production Example 9 From 2-propylindole-6-carboxylic acid methyl ester (500 mg) and benzoyl chloride (970 mg), 3-benzoyl-2-propylindole-methyl was prepared in the same manner as in Production Example 1- (5). 6-carboxylic acid methyl ester (289mg)
Was manufactured. NMR (CDCl3 , δ): 0.82 (3H, t, J = 8Hz), 1.66 (2H, sexte
t, J = 8Hz), 2.78 (2H, t, J = 8Hz), 3.85 (3H, s), 7.29 (1
(H, d, J = 8Hz), 7.49-7.54 (2H, m), 7.60-7.64 (4H, m), 8.
02 (1H, s)
【０１２２】製造例10 ２−プロピルインドール−６−カルボン酸メチルエステ
ル（911mg）のアセトニトリル（15ml）溶液に、撹拌
下、０℃で、クロロスルホニルイソシアナート（0.6
ｇ）のアセトニトリル（1.5ml）溶液を加えた。混合物
を０℃で30分間撹拌し、つぎに、アセトニトリル（15m
l）中のＮ,Ｎ−ジメチルホルムアミド（0.35ｇ）を０℃
で加えた。生じた混合物を20℃で40分間撹拌し、つぎに
水中に注いだ。この混合物を塩化メチレンで３回抽出
し、合せた有機層を硫酸ナトリウムで乾燥し、真空下で
蒸発させた。残留物をシリカゲルクロマトグラフィーに
付し、酢酸エチル−ヘキサン（１：３）混合物で溶出し
て結晶を得て、これを酢酸エチル−ヘキサン混合物から
再結晶して、３−シアノ−２−プロピルインドール−６
−カルボン酸メチルエステル（535mg）を無色結晶とし
て得た。 mp : 148.5−150℃ IR (KBr) : 3251, 2218, 1710, 1284, 1218 cm-1 NMR (CDCl3,δ) : 1.07 (3H,t,J=7Hz), 1.89 (2H,sexte
t,J=7Hz), 3.00 (2H,t,J=7Hz), 3.99 (3H,s), 7.70 (1
H,d,J=7.5Hz), 7.95 (1H,d,J=7.5Hz),8.19 (1H,s), 9.0
5 (1H,br s) MASS (m/z) : 243 (M++1), 76 (bp)Preparation Example 10 A solution of 2-propylindole-6-carboxylic acid methyl ester (911 mg) in acetonitrile (15 ml) was stirred at 0 ° C. under stirring at 0 ° C. for chlorosulfonyl isocyanate (0.6 mg).
A solution of g) in acetonitrile (1.5 ml) was added. The mixture was stirred at 0 ° C. for 30 minutes, then acetonitrile (15 m
l) N, N-dimethylformamide (0.35 g)
Added in. The resulting mixture was stirred at 20 ° C. for 40 minutes and then poured into water. The mixture was extracted three times with methylene chloride, the combined organic layers were dried over sodium sulfate and evaporated under vacuum. The residue was chromatographed on silica gel eluting with an ethyl acetate-hexane (1: 3) mixture to give crystals which were recrystallized from an ethyl acetate-hexane mixture to give 3-cyano-2-propylindole. -6
-Methyl carboxylate (535 mg) was obtained as colorless crystals. mp: 148.5-150 ° C IR (KBr): 3251, 2218, 1710, 1284, 1218 cm-1 NMR (CDCl3 , δ): 1.07 (3H, t, J = 7Hz), 1.89 (2H, sexte
t, J = 7Hz), 3.00 (2H, t, J = 7Hz), 3.99 (3H, s), 7.70 (1
(H, d, J = 7.5Hz), 7.95 (1H, d, J = 7.5Hz), 8.19 (1H, s), 9.0
5 (1H, br s) MASS (m / z): 243 (M+ +1), 76 (bp)
【０１２３】製造例11 ２−エチルインドール−６−カルボン酸メチルエステル
（237mg）と塩化アセチル（0.19ml）とから、製造例１
−(5)と同様にして、３−アセチル−２−エチルインド
ール−６−カルボン酸メチルエステル（106mg）を製造
した。 NMR (CDCl3,δ) : 1.42 (3H,t,J=7Hz), 2.69 (3H,s),
3.27 (2H,q,J=7Hz),3.96 (3H,s), 7.93 (1H,d,J=8Hz),
8.01 (1H,d,J=8Hz), 8.12 (1H,s),8.93 (1H,br s)Production Example 11 Production Example 1 was prepared from 2-ethylindole-6-carboxylic acid methyl ester (237 mg) and acetyl chloride (0.19 ml).
-In the same manner as in (5), 3-acetyl-2-ethylindole-6-carboxylic acid methyl ester (106 mg) was produced. NMR (CDCl3 , δ): 1.42 (3H, t, J = 7Hz), 2.69 (3H, s),
3.27 (2H, q, J = 7Hz), 3.96 (3H, s), 7.93 (1H, d, J = 8Hz),
8.01 (1H, d, J = 8Hz), 8.12 (1H, s), 8.93 (1H, br s)
【０１２４】製造例12 ２−エチルインドール−６−カルボン酸メチルエステル
（317mg）と塩化イソブチリル（0.36ml）とから、製造
例１−(5)と同様にして、２−エチル−３−イソブチリ
ルインドール−６−カルボン酸メチルエステル（200m
g）を製造した。 NMR (CDCl3,δ) : 1.28 (6H,d,J=7Hz), 1.38 (3H,t,J=7
Hz), 3.25 (2H,q,J=7Hz), 3.51 (1H,m), 3.94 (3H,s),
7.92 (2H,s), 8.13 (1H,s), 8.92(1H,br s)Production Example 12 From 2-ethylindole-6-carboxylic acid methyl ester (317 mg) and isobutyryl chloride (0.36 ml), 2-ethyl-3-isobutyric was prepared in the same manner as in Production Example 1- (5). Rilindole-6-carboxylic acid methyl ester (200m
g) was prepared. NMR (CDCl3 , δ): 1.28 (6H, d, J = 7Hz), 1.38 (3H, t, J = 7
Hz), 3.25 (2H, q, J = 7Hz), 3.51 (1H, m), 3.94 (3H, s),
7.92 (2H, s), 8.13 (1H, s), 8.92 (1H, br s)
【０１２５】製造例13 (1) トリフルオロメタンスルホン酸２−ベンジルオキシ
カルボニルアミノ−４−メトキシカルボニルフェニルフ
ェニル（2.1ｇ）とトリブチル（１−プロピニル）スタ
ンナン（2.49ｇ）とから、製造例１−(2)と同様にし
て、３−ベンジルオキシカルボニルアミノ−４−（１−
プロピニル）安息香酸メチルエステル（1.34ｇ）を製造
した。 NMR (CDCl3,δ) : 2.14 (3H,s), 3.91 (3H,s), 5.24 (2
H,s), 7.35-7.50(6H,m), 7.65 (1H,d,J=8Hz), 8.82 (1
H,s) (2) ３−ベンジルオキシカルボニルアミノ−４−（１−
プロピニル）安息香酸メチルエステル（1.32ｇ）から、
製造例１−(3)と同様にして、１−ベンジルオキシカル
ボニル−２−メチルインドール−６−カルボン酸メチル
エステル（1.2ｇ）を製造した。 NMR (CDCl3,δ) : 2.63 (3H,s), 3.89 (3H,s), 5.50 (2
H,s), 6.38 (1H,s),7.35-7.56 (6H,m), 7.91 (1H,d,J=8
Hz), 8.81 (1H,s)Production Example 13 (1) Production Example 1- (2-benzyloxycarbonylamino-4-methoxycarbonylphenylphenyl trifluoromethanesulfonate (2.1 g) and tributyl (1-propynyl) stannane (2.49 g) were prepared. In the same manner as in 2), 3-benzyloxycarbonylamino-4- (1-
Propinyl) benzoic acid methyl ester (1.34 g) was prepared. NMR (CDCl3 , δ): 2.14 (3H, s), 3.91 (3H, s), 5.24 (2
H, s), 7.35-7.50 (6H, m), 7.65 (1H, d, J = 8Hz), 8.82 (1
H, s) (2) 3-benzyloxycarbonylamino-4- (1-
From propynyl) benzoic acid methyl ester (1.32 g)
In the same manner as in Production Example 1- (3), 1-benzyloxycarbonyl-2-methylindole-6-carboxylic acid methyl ester (1.2 g) was produced. NMR (CDCl3 , δ): 2.63 (3H, s), 3.89 (3H, s), 5.50 (2
H, s), 6.38 (1H, s), 7.35-7.56 (6H, m), 7.91 (1H, d, J = 8
Hz), 8.81 (1H, s)
【０１２６】(3) １−ベンジルオキシカルボニル−２−
メチルインドール−６−カルボン酸メチルエステル（1.
18ｇ）から、製造例１−(4)と同様にして、２−メチル
インドール−６−カルボン酸メチルエステル（562mg）
を製造した。 NMR (CDCl3,δ) : 2.49 (3H,s), 3.92 (3H,s), 6.28 (1
H,s), 7.51 (1H,d,J=8Hz), 7.77 (1H,d,J=8Hz), 8.03
(1H,s), 8.12 (1H,br s) (4) ２−メチルインドール−６−カルボン酸メチルエス
テル（305mg）と塩化イソブチリル（0.47ml）とから、
製造例１−(5)と同様にして、３−イソブチリル−２−
メチルインドール−６−カルボン酸メチルエステル（14
2mg）を製造した。 NMR (CDCl3,δ) : 1.26 (6H,d,J=7Hz), 2.81 (3H,s),
3.47 (1H,m), 3.93(3H,s), 7.92 (1H,d,J=8Hz), 8.09
(1H,s), 8.85 (1H,br s)(3) 1-benzyloxycarbonyl-2-
Methyl indole-6-carboxylic acid methyl ester (1.
From 18 g), in the same manner as in Production Example 1- (4), 2-methylindole-6-carboxylic acid methyl ester (562 mg)
Was manufactured. NMR (CDCl3 , δ): 2.49 (3H, s), 3.92 (3H, s), 6.28 (1
H, s), 7.51 (1H, d, J = 8Hz), 7.77 (1H, d, J = 8Hz), 8.03
(1H, s), 8.12 (1H, brs) (4) From 2-methylindole-6-carboxylic acid methyl ester (305 mg) and isobutyryl chloride (0.47 ml),
In the same manner as in Production Example 1- (5), 3-isobutyryl-2-
Methyl indole-6-carboxylic acid methyl ester (14
2 mg). NMR (CDCl3 , δ): 1.26 (6H, d, J = 7Hz), 2.81 (3H, s),
3.47 (1H, m), 3.93 (3H, s), 7.92 (1H, d, J = 8Hz), 8.09
(1H, s), 8.85 (1H, br s)
【０１２７】製造例14 (1) トリフルオロメタンスルホン酸２−ベンジルオキシ
カルボニルアミノ−４−メトキシカルボニルフェニルエ
ステル（7.73ｇ）と（３−メトキシ−１−プロピニル）
トリブチルスタンナン（6.67ｇ）とから、製造例１−
(2)と同様にして、３−ベンジルオキシカルボニルアミ
ノ−４−（３−メトキシ−１−プロピニル）安息香酸メ
チルエステル（4.23ｇ）を製造した。 NMR (CDCl3,δ) : 3.44 (3H,s), 3.91 (3H,s), 4.38 (2
H,s), 5.23 (2H,s),7.3-7.5 (7H,m), 7.69 (1H,d,J=8H
z), 8.82 (1H,s) (2) ３−ベンジルオキシカルボニルアミノ−４−（３−
メトキシ−１−プロピニル）安息香酸メチルエステル
（4.23ｇ）から、製造例１−(3)と同様にして、１−ベ
ンジルオキシカルボニル−２−メトキシメチルインドー
ル−６−カルボン酸メチルエステル（2.14ｇ）を製造し
た。 NMR (CDCl3,δ) : 3.44 (3H,s), 3.88 (3H,s), 4.80 (2
H,s), 5.49 (2H,s),6.70 (1H,s), 7.38-7.58 (6H,m),
7.92 (1H,d,J=8Hz), 8.80 (1H,s)Production Example 14 (1) Trifluoromethanesulfonic acid 2-benzyloxycarbonylamino-4-methoxycarbonylphenyl ester (7.73 g) and (3-methoxy-1-propynyl)
Production Example 1 from tributylstannane (6.67 g)
In the same manner as in (2), methyl 3-benzyloxycarbonylamino-4- (3-methoxy-1-propynyl) benzoate (4.23 g) was produced. NMR (CDCl3 , δ): 3.44 (3H, s), 3.91 (3H, s), 4.38 (2
H, s), 5.23 (2H, s), 7.3-7.5 (7H, m), 7.69 (1H, d, J = 8H
z), 8.82 (1H, s) (2) 3-benzyloxycarbonylamino-4- (3-
From methoxy-1-propynyl) benzoic acid methyl ester (4.23 g), 1-benzyloxycarbonyl-2-methoxymethylindole-6-carboxylic acid methyl ester (2.14 g) in the same manner as in Production Example 1- (3). Was manufactured. NMR (CDCl3 , δ): 3.44 (3H, s), 3.88 (3H, s), 4.80 (2
H, s), 5.49 (2H, s), 6.70 (1H, s), 7.38-7.58 (6H, m),
7.92 (1H, d, J = 8Hz), 8.80 (1H, s)
【０１２８】(3) １−ベンジルオキシカルボニル−２−
メトキシメチルインドール−６−カルボン酸メチルエス
テル（2.12ｇ）から、製造例１−(4)と同様にして、２
−メトキシメチルインドール−６−カルボン酸メチルエ
ステル（0.42ｇ）を製造した。 NMR (CDCl3,δ) : 3.41 (3H,s), 3.94 (3H,s), 4.64 (2
H,s), 6.47 (1H,s),7.59 (1H,d,J=8Hz), 7.80 (1H,d,J=
8Hz), 8.11 (1H,s), 8.59 (1H,br s) (4) ２−メトキシメチルインドール−６−カルボン酸メ
チルエステル（396mg）と塩化イソブチリル（0.53ml）
とから、製造例１−(5)と同様にして、３−イソブチリ
ル−２−メトキシメチルインドール−６−カルボン酸メ
チルエステル（146mg）を製造した。 NMR (CDCl3,δ) : 1.26 (6H,d,J=7Hz), 3.48 (1H,m),
3.58 (3H,s), 3.94(3H,s), 5.03 (2H,s), 7.88 (1H,d,J
=8Hz), 7.96 (1H,d,J=8Hz), 8.18(1H,s), 9.45 (1H,br
s)(3) 1-benzyloxycarbonyl-2-
From methoxymethylindole-6-carboxylic acid methyl ester (2.12 g), 2
-Methoxymethylindole-6-carboxylic acid methyl ester (0.42 g) was prepared. NMR (CDCl3 , δ): 3.41 (3H, s), 3.94 (3H, s), 4.64 (2
H, s), 6.47 (1H, s), 7.59 (1H, d, J = 8Hz), 7.80 (1H, d, J =
8Hz), 8.11 (1H, s), 8.59 (1H, brs) (4) 2-methoxymethylindole-6-carboxylic acid methyl ester (396 mg) and isobutyryl chloride (0.53 ml)
Then, 3-isobutyryl-2-methoxymethylindole-6-carboxylic acid methyl ester (146 mg) was produced in the same manner as in Production Example 1- (5). NMR (CDCl3 , δ): 1.26 (6H, d, J = 7Hz), 3.48 (1H, m),
3.58 (3H, s), 3.94 (3H, s), 5.03 (2H, s), 7.88 (1H, d, J
= 8Hz), 7.96 (1H, d, J = 8Hz), 8.18 (1H, s), 9.45 (1H, br
s)
【０１２９】製造例15 (1) ２−プロピルインドール−６−カルボン酸メチルエ
ステル（300mg）のジクロロメタン（10ml）溶液に、20
℃で、１Ｍ塩化スズ（IV）ジクロロメタン溶液（2.76m
l）を加えた。混合物を20℃で30分間撹拌し、つぎに、
塩化メトキシアセチル（0.25ml）を加えた。20℃で30分
間撹拌後、混合物を酢酸エチルと水とに分配した。有機
層を水および食塩水で洗い、硫酸マグネシウムで乾燥
し、減圧下で蒸発させた。残留物をシリカゲルクロマト
グラフィーに付し、酢酸エチル−ヘキサン（１：10−
１：１）混合物で溶出して、３−メトキシアセチル−２
−プロピルインドール−６−カルボン酸メチルエステル
（135mg）を淡黄色結晶として得た。 mp : 127−129℃ NMR (CDCl3,δ) : 1.05 (3H,t,J=8Hz), 1.83 (2H,sexte
t,J=8Hz), 3.02 (2H,t,J=8Hz), 3.57 (3H,s), 3.97 (3
H,s), 4.72 (2H,s), 7.83 (1H,d,J=8Hz), 7.95 (1H,d,J
=8Hz), 8.18 (1H,s), 9.38 (1H,br s) (2) ３−メトキシアセチル−２−プロピルインドール−
６−カルボン酸メチルエステル（120mg）から、実施例
２と同様にして、３−メトキシアセチル−２−プロピル
インドール−６−カルボン酸（108mg）を製造した。 mp : >250℃ NMR (DMSO-d6,δ) : 0.97 (3H,t,J=8Hz), 1.74 (2H,sex
tet,J=8Hz), 3.09(2H,t,J=8Hz), 3.38 (3H,s), 4.61 (2
H,s), 7.75 (1H,d,J=8Hz), 7.91(1H,d,J=8Hz), 8.00 (1
H,s)Production Example 15 (1) To a solution of methyl 2-propylindole-6-carboxylate (300 mg) in dichloromethane (10 ml) was added 20
At room temperature, 1M tin (IV) chloride dichloromethane solution (2.76m
l) was added. The mixture was stirred at 20 ° C. for 30 minutes, then
Methoxyacetyl chloride (0.25 ml) was added. After stirring at 20 ° C. for 30 minutes, the mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography, and ethyl acetate-hexane (1: 10-
1: 1) elute with the mixture to give 3-methoxyacetyl-2
-Propylindole-6-carboxylic acid methyl ester (135 mg) was obtained as pale yellow crystals. mp: 127-129 ° C NMR (CDCl3 , δ): 1.05 (3H, t, J = 8Hz), 1.83 (2H, sexte
t, J = 8Hz), 3.02 (2H, t, J = 8Hz), 3.57 (3H, s), 3.97 (3
H, s), 4.72 (2H, s), 7.83 (1H, d, J = 8Hz), 7.95 (1H, d, J
= 8Hz), 8.18 (1H, s), 9.38 (1H, brs) (2) 3-methoxyacetyl-2-propylindole-
3-methoxyacetyl-2-propylindole-6-carboxylic acid (108 mg) was produced from 6-carboxylic acid methyl ester (120 mg) in the same manner as in Example 2. mp:> 250 ° C NMR (DMSO-d6 , δ): 0.97 (3H, t, J = 8Hz), 1.74 (2H, sex
tet, J = 8Hz), 3.09 (2H, t, J = 8Hz), 3.38 (3H, s), 4.61 (2
H, s), 7.75 (1H, d, J = 8Hz), 7.91 (1H, d, J = 8Hz), 8.00 (1
H, s)
【０１３０】(3) ３−メトキシアセチル−２−プロピル
インドール−６−カルボン酸（95mg）から、実施例６と
同様にして、３−メトキシアセチル−２−プロピルイン
ドール−６−カルボキサミド（89mg）を製造した。 mp : 165−167℃ NMR (DMSO-d6,δ) : 0.95 (3H,t,J=8Hz), 1.74 (2H,sex
tet,J=8Hz), 3.06(2H,t,J=8Hz), 3.38 (3H,s), 4.60 (2
H,s), 7.25 (1H,br s), 7.70 (1H,d,J=8Hz), 7.84 (1H,
d,J=8Hz), 7.94 (1H,s), 7.97 (1H,br s)(3) From 3-methoxyacetyl-2-propylindole-6-carboxylic acid (95 mg), 3-methoxyacetyl-2-propylindole-6-carboxamide (89 mg) was prepared in the same manner as in Example 6. Manufactured. mp: 165-167 ° C NMR (DMSO-d6 , δ): 0.95 (3H, t, J = 8Hz), 1.74 (2H, sex
tet, J = 8Hz), 3.06 (2H, t, J = 8Hz), 3.38 (3H, s), 4.60 (2
H, s), 7.25 (1H, br s), 7.70 (1H, d, J = 8Hz), 7.84 (1H, br
d, J = 8Hz), 7.94 (1H, s), 7.97 (1H, brs)
【０１３１】製造例16 ２−アミノ−３−ヒドロキシ安息香酸メチルエステル
（882mg）のピリジン(２ml)溶液に、無水酢酸（1.2ml）
を加え、混合物を20℃で18時間撹拌した。反応混合物を
ジイソプロピルエーテルで希釈し、生じた固体を採取
し、ジイソプロピルエーテルで洗った。この固体をジイ
ソプロピルエーテル中で粉末化して、２−アセトアミド
−３−アセトキシ安息香酸メチルエステル（1.25ｇ）を
固体として得た。 NMR (CDCl3,δ) : 2.18 (3H,s), 2.26 (3H,s), 3.90 (3
H,s), 7.27 (1H,t,J=8Hz), 7.39 (1H,d,J=8Hz), 7.83
(1H,d,J=8Hz), 9.09 (1H,br s)Production Example 16 Acetic anhydride (1.2 ml) was added to a solution of 2-amino-3-hydroxybenzoic acid methyl ester (882 mg) in pyridine (2 ml).
Was added and the mixture was stirred at 20 ° C. for 18 hours. The reaction mixture was diluted with diisopropyl ether, and the resulting solid was collected and washed with diisopropyl ether. This solid was triturated in diisopropyl ether to give 2-acetamido-3-acetoxybenzoic acid methyl ester (1.25 g) as a solid. NMR (CDCl3 , δ): 2.18 (3H, s), 2.26 (3H, s), 3.90 (3
H, s), 7.27 (1H, t, J = 8Hz), 7.39 (1H, d, J = 8Hz), 7.83
(1H, d, J = 8Hz), 9.09 (1H, br s)
【０１３２】製造例17 製造例16と同様にして、次の(1)〜(4)に記載の化合物を
製造した。 (1) ３−アセトアミド−４−アセトキシ安息香酸メチル
エステル NMR (CDCl3,δ) : 2.21 (3H,s), 2.37 (3H,s), 3.93 (3
H,s), 7.22 (1H,d,J=8Hz), 7.83 (1H,d,J=8Hz), 8.22
(1H,s) (2) ４−アセトアミド−３−アセトキシ安息香酸メチル
エステル NMR (DMSO-d6,δ) : 2.12 (3H,s), 2.33 (3H,s), 3.84
(3H,s), 7.73 (1H,d,J=2Hz), 7.82 (1H,dd,J=2, 8Hz),
8.22 (1H,d,J=8Hz), 9.64 (1H,s)Production Example 17 The following compounds (1) to (4) were produced in the same manner as in Production Example 16. (1) 3-acetamido-4-acetoxybenzoic acid methyl ester NMR (CDCl3 , δ): 2.21 (3H, s), 2.37 (3H, s), 3.93 (3
H, s), 7.22 (1H, d, J = 8Hz), 7.83 (1H, d, J = 8Hz), 8.22
(1H, s) (2) 4-acetamido-3-acetoxybenzoic acid methyl ester NMR (DMSO-d6 , δ): 2.12 (3H, s), 2.33 (3H, s), 3.84
(3H, s), 7.73 (1H, d, J = 2Hz), 7.82 (1H, dd, J = 2,8Hz),
8.22 (1H, d, J = 8Hz), 9.64 (1H, s)
【０１３３】(3) ３−アセトアミド−２−アセトキシ安
息香酸メチルエステル NMR (CDCl3,δ) : 2.20 (3H,s), 2.43 (3H,s), 3.91 (3
H,s), 7.29 (1H,t,J=8Hz), 7.74 (1H,d,J=8Hz), 8.51
(1H,d,J=8Hz) (4) ３−アセトアミド−４−トリフルオロメタンスルホ
ニルオキシフェニル酢酸メチルエステル mp : 68.5−70℃ IR (KBr) : 3341, 1727, 1699, 1437, 1425 cm-1 NMR (CDCl3,δ) : 2.24 (3H,s), 3.68 (3H,s), 3.73 (3
H,s), 7.11 (1H,dd,J=8, 1Hz), 7.24-7.30 (2H,m), 8.1
9 (1H,s) MASS (m/z) : 354 (M+-1), 149 (bp)(3) 3-acetamido-2-acetoxybenzoic acid methyl ester NMR (CDCl3 , δ): 2.20 (3H, s), 2.43 (3H, s), 3.91 (3
H, s), 7.29 (1H, t, J = 8Hz), 7.74 (1H, d, J = 8Hz), 8.51
(1H, d, J = 8Hz) (4) 3-acetamido-4-trifluoromethanesulfonyloxyphenylacetic acid methyl ester mp: 68.5-70 ° C IR (KBr): 3341, 1727, 1699, 1437, 1425 cm-1 NMR (CDCl3 , δ): 2.24 (3H, s), 3.68 (3H, s), 3.73 (3
H, s), 7.11 (1H, dd, J = 8,1Hz), 7.24-7.30 (2H, m), 8.1
9 (1H, s) MASS (m / z): 354 (M+ -1), 149 (bp)
【０１３４】製造例18 ２−アセトアミド−３−アセトキシ安息香酸メチルエス
テル（1.72ｇ）のメタノール（９ml）溶液に、粉末炭酸
カリウム（1.4ｇ）を加え、混合物を20分間撹拌した。
生じた固体を濾別し、メタノールで洗った。濾液を減圧
下で蒸発させ、残留物を１Ｎ塩酸で酸性化し、酢酸エチ
ルで抽出した。有機層を食塩水で洗い、硫酸ナトリウム
で乾燥し、減圧下で蒸発させた。残留物をイソプロピル
エーテルとヘキサンとの混合物を用いて粉末化して、２
−アセトアミド−３−ヒドロキシ安息香酸メチルエステ
ル（1.21ｇ）を固体として得た。 NMR (CDCl3,δ) : 2.33 (3H,s), 3.93 (3H,s), 7.14 (1
H,t,J=8Hz), 7.23(1H,d,J=8Hz), 7.61 (1H,d,J=8Hz),
9.88 (1H,s)Production Example 18 Powdered potassium carbonate (1.4 g) was added to a solution of 2-acetamido-3-acetoxybenzoic acid methyl ester (1.72 g) in methanol (9 ml), and the mixture was stirred for 20 minutes.
The resulting solid was filtered off and washed with methanol. The filtrate was evaporated under reduced pressure, the residue was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue is triturated with a mixture of isopropyl ether and hexane to give 2
-Acetamide-3-hydroxybenzoic acid methyl ester (1.21 g) was obtained as a solid. NMR (CDCl3 , δ): 2.33 (3H, s), 3.93 (3H, s), 7.14 (1
H, t, J = 8Hz), 7.23 (1H, d, J = 8Hz), 7.61 (1H, d, J = 8Hz),
9.88 (1H, s)
【０１３５】製造例19 製造例18と同様にして、次の(1)〜(3)に記載の化合物を
製造した。 (1) ３−アセトアミド−４−ヒドロキシ安息香酸メチル
エステル NMR (DMSO-d6,δ) : 2.11 (3H,s), 3.80 (3H,s), 6.93
(1H,d,J=8Hz), 7.56(1H,d,J=2Hz), 8.47 (1H,s), 9.20
(1H,s) (2) ４−アセトアミド−３−ヒドロキシ安息香酸メチル
エステル NMR (DMSO-d6,δ) : 2.14 (3H,s), 3.78 (3H,s), 7.37
(1H,dd,J=2, 8Hz),7.45 (1H,d,J=2Hz), 8.08 (1H,d,J=8
Hz), 9.32 (1H,s) (3) ３−アセトアミド−２−ヒドロキシ安息香酸メチル
エステル NMR (CDCl3,δ) : 2.33 (3H,s), 4.97 (3H,s), 6.90 (1
H,t,J=8Hz), 7.56(1H,d,J=8Hz), 7.81 (1H,br s), 8.57
(1H,d,J=8Hz)Preparation Example 19 The following compounds (1) to (3) were prepared in the same manner as in Preparation Example 18. (1) 3-acetamido-4-hydroxybenzoic acid methyl esterNMR (DMSO-d 6, δ ): 2.11 (3H, s), 3.80 (3H, s), 6.93
(1H, d, J = 8Hz), 7.56 (1H, d, J = 2Hz), 8.47 (1H, s), 9.20
(1H, s) (2) 4-acetamido-3-hydroxybenzoic acid methyl ester NMR (DMSO-d6 , δ): 2.14 (3H, s), 3.78 (3H, s), 7.37
(1H, dd, J = 2,8Hz), 7.45 (1H, d, J = 2Hz), 8.08 (1H, d, J = 8
Hz), 9.32 (1H, s) (3) 3-acetamido-2-hydroxybenzoic acid methyl ester NMR (CDCl3 , δ): 2.33 (3H, s), 4.97 (3H, s), 6.90 (1
(H, t, J = 8Hz), 7.56 (1H, d, J = 8Hz), 7.81 (1H, br s), 8.57
(1H, d, J = 8Hz)
【０１３６】製造例20 ２−アセトアミド−３−ヒドロキシ安息香酸メチルエス
テル（1.2ｇ）のピリジン（1.4ml）およびジクロロメタ
ン（２ml）混合物溶液に、トリフルオロメタンスルホン
酸無水物（1.1ml）を０℃で徐々に加えた。添加完了
後、混合物を20℃で20分間撹拌する。生じた混合物を氷
上に注ぎ、酢酸エチルで抽出した。有機層を１Ｎ塩酸、
炭酸ナトリウム水溶液および食塩水で洗い、硫酸ナトリ
ウムで乾燥し、減圧下で蒸発させた。残留物をジクロロ
メタンとヘキサンとの混合溶液を用いて粉末化して、２
−アセトアミド−３−トリフルオロメタンスルホニルオ
キシ安息香酸メチルエステル（1.78ｇ）を固体として得
た。 NMR (CDCl3,δ) : 2.24 (3H,s), 3.93 (3H,s), 7.34 (1
H,t,J=8Hz), 7.49(1H,d,J=8Hz), 7.99 (1H,d,J=8Hz),
8.90 (1H,br s)Production Example 20 To a solution of a mixture of 2-acetamido-3-hydroxybenzoic acid methyl ester (1.2 g) in pyridine (1.4 ml) and dichloromethane (2 ml) was added trifluoromethanesulfonic anhydride (1.1 ml) at 0 ° C. Slowly added. After the addition is complete, the mixture is stirred at 20 ° C. for 20 minutes. The resulting mixture was poured on ice and extracted with ethyl acetate. The organic layer is 1N hydrochloric acid,
Washed with aqueous sodium carbonate and brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was triturated with a mixed solution of dichloromethane and hexane,
-Acetamide-3-trifluoromethanesulfonyloxybenzoic acid methyl ester (1.78 g) was obtained as a solid. NMR (CDCl3 , δ): 2.24 (3H, s), 3.93 (3H, s), 7.34 (1
H, t, J = 8Hz), 7.49 (1H, d, J = 8Hz), 7.99 (1H, d, J = 8Hz),
8.90 (1H, br s)
【０１３７】製造例21 製造例20と同様にして、次の(1)〜(4)に記載の化合物を
製造した。 (1) ３−アセトアミド−４−トリフルオロメタンスルホ
ニルオキシ安息香酸メチルエステル NMR (CDCl3,δ) : 2.25 (3H,s), 3.93 (3H,s), 7.37 (1
H,d,J=8Hz), 7.92(1H,m), 8.86 (1H,br s) (2) ４−アセトアミド−３−トリフルオロメタンスルホ
ニルオキシ安息香酸メチルエステル NMR (CDCl3,δ) : 2.27 (3H,s), 3.94 (3H,s), 7.51 (1
H,br s), 7.94 (1H,d,J=2Hz), 8.05 (1H,dd,J=2, 8Hz),
8.47 (1H,d,J=8Hz)Production Example 21 The following compounds (1) to (4) were produced in the same manner as in Production Example 20. (1) 3-acetamido-4-trifluoromethanesulfonyloxybenzoic acid methyl ester NMR (CDCl3 , δ): 2.25 (3H, s), 3.93 (3H, s), 7.37 (1
(H, d, J = 8Hz), 7.92 (1H, m), 8.86 (1H, brs) (2) 4-acetamido-3-trifluoromethanesulfonyloxybenzoic acid methyl ester NMR (CDCl3 , δ): 2.27 ( 3H, s), 3.94 (3H, s), 7.51 (1
H, br s), 7.94 (1H, d, J = 2Hz), 8.05 (1H, dd, J = 2,8Hz),
8.47 (1H, d, J = 8Hz)
【０１３８】(3) ３−アセトアミド−２−トリフルオロ
メタンスルホニルオキシ安息香酸メチルエステル NMR (CDCl3,δ) : 2.23 (3H,s), 3.93 (3H,s), 7.40 (1
H,br s), 7.43 (1H,t,J=8Hz), 7.76 (1H,d,J=8Hz), 8.3
9 (1H,d,HJ=8Hz) (4) ３−ニトロ−４−トリフルオロメタンスルホニルオ
キシフェニル酢酸メチルエステル mp : 44−45℃ IR (KBr) : 1736, 1544, 1434, 1340 cm-1 NMR (CDCl3,δ) : 3.75 (2H,s), 3.76 (3H,s), 7.41 (1
H,d,J=8Hz), 7.68(1H,dd,J=8, 1Hz), 8.10 (1H,d,J=1H
z) MASS (m/z) : 343 (M+), 135 (bp)(3) 3-acetamido-2-trifluoromethanesulfonyloxybenzoic acid methyl ester NMR (CDCl3 , δ): 2.23 (3H, s), 3.93 (3H, s), 7.40 (1
H, brs), 7.43 (1H, t, J = 8Hz), 7.76 (1H, d, J = 8Hz), 8.3
9 (1H, d, HJ = 8Hz) (4) 3-Nitro-4-trifluoromethanesulfonyloxyphenylacetic acid methyl ester mp: 44-45 ° C IR (KBr): 1736, 1544, 1434, 1340 cm-1 NMR ( CDCl3 , δ): 3.75 (2H, s), 3.76 (3H, s), 7.41 (1
H, d, J = 8Hz), 7.68 (1H, dd, J = 8,1Hz), 8.10 (1H, d, J = 1H
z) MASS (m / z): 343 (M+ ), 135 (bp)
【０１３９】製造例22 製造例１−(2)と同様にして、次の(1)〜(3)に記載の化
合物を製造した。 (1) ２−アセトアミド−３−（１−ペンチニル）安息香
酸メチルエステル NMR (CDCl3,δ) : 1.06 (3H,t,J=7Hz), 1.64 (2H,m),
2.20 (3H,s), 2.43(2H,t,J=7Hz), 3.88 (3H,s), 7.16
(1H,t,J=8Hz), 7.57 (1H,d,J=8Hz),7.76 (1H,d,J=8Hz),
8.42 (1H,br s) (2) ４−アセトアミド−３−（１−ペンチニル）安息香
酸メチルエステル NMR (CDCl3,δ) : 1.11 (3H,t,J=8Hz), 1.68 (2H,sexte
t,J=8Hz), 2.24 (3H,s), 2.52 (2H,t,J=8Hz), 3.89 (3
H,s), 7.94 (1H,dd,J=1, 8Hz), 8.07(1H,d,J=1Hz), 8.1
2 (1H,br s), 8.48 (1H,d,J=8Hz)Production Example 22 The following compounds (1) to (3) were produced in the same manner as in Production Example 1- (2). (1) 2-acetamido-3- (1-pentynyl) benzoic acid methyl ester NMR (CDCl3 , δ): 1.06 (3H, t, J = 7Hz), 1.64 (2H, m),
2.20 (3H, s), 2.43 (2H, t, J = 7Hz), 3.88 (3H, s), 7.16
(1H, t, J = 8Hz), 7.57 (1H, d, J = 8Hz), 7.76 (1H, d, J = 8Hz),
8.42 (1H, brs) (2) 4-acetamido-3- (1-pentynyl) benzoic acid methyl ester NMR (CDCl3 , δ): 1.11 (3H, t, J = 8Hz), 1.68 (2H, sexte
t, J = 8Hz), 2.24 (3H, s), 2.52 (2H, t, J = 8Hz), 3.89 (3
H, s), 7.94 (1H, dd, J = 1,8Hz), 8.07 (1H, d, J = 1Hz), 8.1
2 (1H, br s), 8.48 (1H, d, J = 8Hz)
【０１４０】(3) ３−アセトアミド−２−（１−ペンチ
ニル）安息香酸メチルエステル NMR (CDCl3,δ) : 1.12 (3H,t,J=7Hz), 1.73 (2H,m),
2.22 (3H,s), 2.59(2H,t,J=7Hz), 3.91 (3H,s), 7.32
(1H,t,J=8Hz), 7.63 (1H,d,J=8Hz),8.29 (1H,br s), 8.
62 (1H,d,J=8Hz)(3) 3-acetamido-2- (1-pentynyl) benzoic acid methyl ester NMR (CDCl3 , δ): 1.12 (3H, t, J = 7Hz), 1.73 (2H, m),
2.22 (3H, s), 2.59 (2H, t, J = 7Hz), 3.91 (3H, s), 7.32
(1H, t, J = 8Hz), 7.63 (1H, d, J = 8Hz), 8.29 (1H, brs), 8.
62 (1H, d, J = 8Hz)
【０１４１】製造例23 ３−アセトアミド−４−トリフルオロメタンスルホニル
オキシ安息香酸メチルエステル（1.43ｇ）、５−ヘキシ
ン酸メチルエステル（582mg）、塩化パラジウム（II）
（14.9mg）、トリフェニルホスフィン（43.8mg）および
塩化銅（Ｉ）（32mg）のジエチルアミン（18ml）中の混
合物を、20℃で14時間撹拌した。減圧下で溶媒を蒸発さ
せ、残留物をシリカゲルクロマトグラフィーに付し、ヘ
キサン−酢酸エチル（１：２）混合物で溶出して、３−
アセトアミド−４−（５−メトキシカルボニル−１−ペ
ンチニル）安息香酸メチルエステル（1.15ｇ）を無色結
晶として得た。 NMR (CDCl3,δ) : 2.02 (2H,m), 2.27 (3H,s), 2.53 (2
H,t,J=7Hz), 2.63(2H,t,J=7Hz), 3.68 (3H,s), 3.90 (3
H,s), 7.41 (1H,d,J=8Hz), 7.70(1H,d,J=8Hz), 8.00 (1
H,br s), 8.98 (1H,br s)Production Example 23 Methyl 3-acetamido-4-trifluoromethanesulfonyloxybenzoate (1.43 g), methyl 5-hexyne (582 mg), palladium (II) chloride
(14.9 mg), a mixture of triphenylphosphine (43.8 mg) and copper (I) chloride (32 mg) in diethylamine (18 ml) was stirred at 20 ° C. for 14 hours. The solvent was evaporated under reduced pressure and the residue was chromatographed on silica gel, eluting with a hexane-ethyl acetate (1: 2) mixture to give 3-
Acetamide-4- (5-methoxycarbonyl-1-pentynyl) benzoic acid methyl ester (1.15 g) was obtained as colorless crystals. NMR (CDCl3 , δ): 2.02 (2H, m), 2.27 (3H, s), 2.53 (2
H, t, J = 7Hz), 2.63 (2H, t, J = 7Hz), 3.68 (3H, s), 3.90 (3
H, s), 7.41 (1H, d, J = 8Hz), 7.70 (1H, d, J = 8Hz), 8.00 (1
H, br s), 8.98 (1H, br s)
【０１４２】製造例24 製造例23と同様にして、次の(1)〜(3)に記載の化合物を
製造した。 (1) ３−アセトアミド−４−（１−ペンチニル）安息香
酸メチルエステル NMR (CDCl3,δ) : 1.12 (3H,t,J=7Hz), 1.65 (2H,m),
2.23 (3H,s), 2.54(2H,t,J=7Hz), 3.90 (3H,s), 7.43
(1H,dd,J=1, 8Hz), 7.70 (1H,m),7.95 (1H,br s), 8.98
(1H,br s) (2) ３−アセトアミド−４−（４−メトキシカルボニル
−１−ブチニル）安息香酸メチルエステル NMR (CDCl3,δ) : 2.32 (3H,s), 2.68 (2H,m), 2.80 (2
H,m), 3.73 (3H,s),3.89 (3H,s), 7.38 (1H,d,J=8Hz),
7.67 (1H,m), 8.28 (1H,br s), 9.04(1H,br s)Preparation Example 24 The following compounds (1) to (3) were prepared in the same manner as in Preparation Example 23. (1) 3-acetamido-4- (1-pentynyl) benzoic acid methyl ester NMR (CDCl3 , δ): 1.12 (3H, t, J = 7Hz), 1.65 (2H, m),
2.23 (3H, s), 2.54 (2H, t, J = 7Hz), 3.90 (3H, s), 7.43
(1H, dd, J = 1,8Hz), 7.70 (1H, m), 7.95 (1H, br s), 8.98
(1H, brs) (2) 3-acetamido-4- (4-methoxycarbonyl-1-butynyl) benzoic acid methyl ester NMR (CDCl3 , δ): 2.32 (3H, s), 2.68 (2H, m) , 2.80 (2
H, m), 3.73 (3H, s), 3.89 (3H, s), 7.38 (1H, d, J = 8Hz),
7.67 (1H, m), 8.28 (1H, br s), 9.04 (1H, br s)
【０１４３】(3) ３−アセトアミド−４−（１−ペンチ
ニル）フェニル酢酸メチルエステル mp : 77−78℃ IR (KBr) : 3293, 1739, 1699, 1665, 1428 cm-1 NMR (CDCl3,δ) : 1.09 (3H,t,J=7Hz), 1.69 (2H,sexte
t,J=7Hz), 2.22(3H,s), 2.49 (2H,t,J=7Hz), 3.64 (2H,
s), 3.70 (3H,s), 6.94 (1H,d,J=7.5Hz), 7.31 (1H,d,J
=7.5Hz), 7.93 (1H,br s), 8.33 (1H,s) MASS (m/z) : 274 (M++1, bp)(3) 3-acetamido-4- (1-pentynyl) phenylacetic acid methyl ester mp: 77-78 ° C IR (KBr): 3293, 1739, 1699, 1665, 1428 cm-1 NMR (CDCl3 , δ ): 1.09 (3H, t, J = 7Hz), 1.69 (2H, sexte
t, J = 7Hz), 2.22 (3H, s), 2.49 (2H, t, J = 7Hz), 3.64 (2H,
s), 3.70 (3H, s), 6.94 (1H, d, J = 7.5Hz), 7.31 (1H, d, J
= 7.5Hz), 7.93 (1H, br s), 8.33 (1H, s) MASS (m / z): 274 (M+ +1, bp)
【０１４４】製造例25 製造例１−(3)と同様にして、次の(1)〜(7)に記載の化
合物を製造した。 (1) １−アセチル−２−（３−メトキシカルボニルプロ
ピル）インドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 2.08 (2H,m), 2.43 (2H,t,J=7Hz),
2.86 (3H,s), 3.12(2H,t,J=7Hz), 3.67 (3H,s), 3.94
(3H,s), 6.49 (1H,s), 7.52 (1H,d,J=8Hz), 7.93 (1H,
d,J=8Hz), 8.47 (1H,s) (2) １−アセチル−２−プロピルインドール−７−カル
ボン酸メチルエステル NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.78 (2H,m),
2.39 (3H,s), 2.79(2H,m), 3.91 (3H,s), 6.38 (1H,m),
7.23 (1H,t,J=8Hz), 7.68 (1H,d,J=8Hz), 7.79 (1H,d,
J=8Hz)Production Example 25 The following compounds (1) to (7) were produced in the same manner as in Production Example 1- (3). (1) 1-acetyl-2- (3-methoxycarbonylpropyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.08 (2H, m), 2.43 (2H, t, J = 7Hz),
2.86 (3H, s), 3.12 (2H, t, J = 7Hz), 3.67 (3H, s), 3.94
(3H, s), 6.49 (1H, s), 7.52 (1H, d, J = 8Hz), 7.93 (1H,
d, J = 8Hz), 8.47 (1H, s) (2) 1- acetyl-2-propyl-indole-7-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.04 (3H, t, J = 7Hz), 1.78 (2H, m),
2.39 (3H, s), 2.79 (2H, m), 3.91 (3H, s), 6.38 (1H, m),
7.23 (1H, t, J = 8Hz), 7.68 (1H, d, J = 8Hz), 7.79 (1H, d,
(J = 8Hz)
【０１４５】(3) １−アセチル−２−プロピルインドー
ル−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.06 (3H,t,J=7Hz), 1.77 (2H,m),
2.82 (3H,s), 3.03(2H,t,J=8Hz), 3.94 (3H,s), 6.47
(1H,s), 7.49 (1H,d,J=8Hz), 7.94(1H,d,J=8Hz), 8.53
(1H,s) (4) １−アセチル−２−プロピルインドール−５−カル
ボン酸メチルエステル NMR (CDCl3,δ) : 1.05 (3H,t,J=8Hz), 1.75 (2H,sexte
t,J=8Hz), 2.76 (3H,s), 2.98 (2H,t,J=8Hz), 3.94 (3
H,s), 6.48 (1H,d,J=1Hz), 7.87 (1H,d,J=8Hz), 7.95
(1H,d,J=8Hz), 8.18 (1H,s)(3) 1-acetyl-2-propylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.06 (3H, t, J = 7 Hz), 1.77 (2H, m),
2.82 (3H, s), 3.03 (2H, t, J = 8Hz), 3.94 (3H, s), 6.47
(1H, s), 7.49 (1H, d, J = 8Hz), 7.94 (1H, d, J = 8Hz), 8.53
(1H, s) (4) 1-acetyl-2-propylindole-5-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.05 (3H, t, J = 8Hz), 1.75 (2H, sexte
t, J = 8Hz), 2.76 (3H, s), 2.98 (2H, t, J = 8Hz), 3.94 (3
H, s), 6.48 (1H, d, J = 1Hz), 7.87 (1H, d, J = 8Hz), 7.95
(1H, d, J = 8Hz), 8.18 (1H, s)
【０１４６】(5) １−アセチル−２−プロピルインドー
ル−４−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.07 (3H,t,J=7Hz), 1.80 (2H,m),
2.76 (3H,s), 3.01(2H,t,J=7Hz), 3.97 (3H,s), 7.18
(1H,s), 7.28 (1H,t,J=8Hz), 8.06(1H,d,J=8Hz), 8.15
(1H,d,J=8Hz) (6) １−アセチル−２−（２−メトキシカルボニルエチ
ル）インドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 2.78 (2H,t,J=7Hz), 2.87 (3H,s),
3.39 (2H,t,J=7Hz),3.68 (3H,s), 3.94 (3H,s), 6.49
(1H,s), 7.52 (1H,d,J=8Hz), 7.93(1H,d,J=8Hz), 8.46
(1H,s)(5) 1-acetyl-2-propylindole-4-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.07 (3H, t, J = 7 Hz), 1.80 (2H, m),
2.76 (3H, s), 3.01 (2H, t, J = 7Hz), 3.97 (3H, s), 7.18
(1H, s), 7.28 (1H, t, J = 8Hz), 8.06 (1H, d, J = 8Hz), 8.15
(1H, d, J = 8 Hz) (6) 1-acetyl-2- (2-methoxycarbonylethyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.78 (2H, t, J = 7 Hz) ), 2.87 (3H, s),
3.39 (2H, t, J = 7Hz), 3.68 (3H, s), 3.94 (3H, s), 6.49
(1H, s), 7.52 (1H, d, J = 8Hz), 7.93 (1H, d, J = 8Hz), 8.46
(1H, s)
【０１４７】(7) １−アセチル−２−プロピルインドー
ル−６−イル酢酸メチルエステル mp : 85−87℃ IR (KBr) : 1736, 1700, 1376, 1320, 1303 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.74 (2H,sexte
t,J=7Hz), 2.75(3H,s), 2.96 (2H,t,J=7Hz), 3.70 (2H,
s), 3.75 (3H,s), 6.40 (1H,s),7.14 (1H,d,J=8Hz), 7.
43 (1H,d,J=8Hz), 7.81 (1H,s) MASS (m/z) : 274 (M++1), 74 (bp)(7) 1-acetyl-2-propylindol-6-ylacetic acid methyl ester mp: 85-87 ° C. IR (KBr): 1736, 1700, 1376, 1320, 1303 cm-1 NMR (CDCl3 , δ ): 1.04 (3H, t, J = 7Hz), 1.74 (2H, sexte
t, J = 7Hz), 2.75 (3H, s), 2.96 (2H, t, J = 7Hz), 3.70 (2H,
s), 3.75 (3H, s), 6.40 (1H, s), 7.14 (1H, d, J = 8Hz), 7.
43 (1H, d, J = 8Hz), 7.81 (1H, s) MASS (m / z): 274 (M+ +1), 74 (bp)
【０１４８】製造例26 １−アセチル−２−（３−メトキシカルボニルプロピ
ル）インドール−６−カルボン酸メチルエステル（2.34
ｇ）のメタノール（20ml）溶液に、粉末炭酸カリウム
（1.04ｇ）を加え、混合物を還流下に10分間撹拌した。
生じた混合物を減圧下で蒸発させ、残留物を１Ｎ塩酸で
酸性化し、クロロホルムで抽出した。有機層を炭酸ナト
リウム水溶液および食塩水で洗い、硫酸ナトリウムで乾
燥し、減圧下で蒸発させた。残留物をエーテルで粉末化
して、２−（３−メトキシカルボニルプロピル）インド
ール−６−カルボン酸メチルエステル（1.23ｇ）を固体
として得た。 NMR (CDCl3,δ) : 2.07 (2H,m), 2.42 (2H,t,J=7Hz),
2.84 (2H,t,J=7Hz),3.68 (3H,s), 3.92 (3H,s), 6.31
(1H,s), 7.52 (1H,d,J=8Hz), 7.78(1H,d,J=8Hz), 8.07
(1H,s), 8.39 (1H,br s)Production Example 26 1-acetyl-2- (3-methoxycarbonylpropyl) indole-6-carboxylic acid methyl ester (2.34
To a solution of g) in methanol (20 ml) was added powdered potassium carbonate (1.04 g) and the mixture was stirred at reflux for 10 minutes.
The resulting mixture was evaporated under reduced pressure, the residue was acidified with 1N hydrochloric acid and extracted with chloroform. The organic layer was washed with aqueous sodium carbonate and brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was triturated with ether to give 2- (3-methoxycarbonylpropyl) indole-6-carboxylic acid methyl ester (1.23 g) as a solid. NMR (CDCl3 , δ): 2.07 (2H, m), 2.42 (2H, t, J = 7Hz),
2.84 (2H, t, J = 7Hz), 3.68 (3H, s), 3.92 (3H, s), 6.31
(1H, s), 7.52 (1H, d, J = 8Hz), 7.78 (1H, d, J = 8Hz), 8.07
(1H, s), 8.39 (1H, br s)
【０１４９】製造例27 製造例26と同様にして、次の(1)〜(5)に記載の化合物を
製造した。 (1) ２−プロピルインドール−７−カルボン酸メチルエ
ステル NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.78 (2H,m),
2.78 (2H,t,J=7Hz),3.98 (3H,s), 6.28 (1H,m), 7.09
(1H,t,J=8Hz), 7.72 (1H,d,J=8Hz),7.79 (1H,d,J=8Hz),
9.58 (1H,br s) (2) ２−プロピルインドール−６−カルボン酸メチルエ
ステルProduction Example 27 The following compounds (1) to (5) were produced in the same manner as in Production Example 26. (1) 2-propylindole-7-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.78 (2H, m),
2.78 (2H, t, J = 7Hz), 3.98 (3H, s), 6.28 (1H, m), 7.09
(1H, t, J = 8Hz), 7.72 (1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz),
9.58 (1H, brs) (2) 2-propylindole-6-carboxylic acid methyl ester
【０１５０】(3) ２−プロピルインドール−５−カルボ
ン酸メチルエステル NMR (CDCl3,δ) : 1.02 (3H,t,J=8Hz), 1.76 (2H,sexte
t,J=8Hz), 2.74(2H,t,J=8Hz), 3.92 (3H,s), 6.33 (1H,
d,J=1Hz), 7.28 (1H,d,J=8Hz),7.73 (1H,d,J=8Hz), 8.1
0 (1H,br s), 8.28 (1H,s) (4) ２−プロピルインドール−４−カルボン酸メチルエ
ステル NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.80 (2H,m),
2.78 (2H,m), 3.98(3H,s), 6.89 (1H,s), 7.14 (1H,t,J
=8Hz), 7.48 (1H,d,J=8Hz), 7.84(1H,d,J=8Hz), 8.08
(1H,br s)(3) 2-propylindole-5-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.02 (3H, t, J = 8 Hz), 1.76 (2H, sexte
t, J = 8Hz), 2.74 (2H, t, J = 8Hz), 3.92 (3H, s), 6.33 (1H,
d, J = 1Hz), 7.28 (1H, d, J = 8Hz), 7.73 (1H, d, J = 8Hz), 8.1
0 (1H, brs), 8.28 (1H, s) (4) 2-propylindole-4-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.80 (2H , m),
2.78 (2H, m), 3.98 (3H, s), 6.89 (1H, s), 7.14 (1H, t, J
= 8Hz), 7.48 (1H, d, J = 8Hz), 7.84 (1H, d, J = 8Hz), 8.08
(1H, br s)
【０１５１】(5) ２−（２−メトキシカルボニルエチ
ル）インドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 2.78 (2H,m), 3.10 (2H,m), 3.73 (3
H,s), 3.93 (3H,s),6.30 (1H,s), 7.53 (1H,d,J=8Hz),
7.76 (1H,d,J=8Hz), 8.08 (1H,s),8.88 (1H,br s)(5) 2- (2-methoxycarbonylethyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.78 (2H, m), 3.10 (2H, m), 3.73 (3
H, s), 3.93 (3H, s), 6.30 (1H, s), 7.53 (1H, d, J = 8Hz),
7.76 (1H, d, J = 8Hz), 8.08 (1H, s), 8.88 (1H, br s)
【０１５２】製造例28 製造例１−(5)と同様にして、次の(1)〜(19)に記載の化
合物を製造した。 (1) ３−イソブチリル−２−プロピルインドール−７−
カルボン酸メチルエステル NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.27 (6H,d,J=7
Hz), 1.82 (2H,m),3.26 (2H,m), 3.47 (1H,m), 3.99 (3
H,s), 7.28 (1H,t,J=8Hz), 7.85(1H,d,J=8Hz), 8.18 (1
H,s) (2) ３−イソブチリル−２−プロピルインドール−５−
カルボン酸メチルエステル NMR (CDCl3,δ) : 1.04 (3H,t,J=8Hz), 1.28 (6H,d,J=8
Hz), 1.78 (2H,sextet,J=8Hz), 3.15 (2H,t,J=8Hz), 3.
56 (1H,septet,J=8Hz), 3.96(3H,s), 7.37 (1H,d,J=1H
z), 7.93 (1H,dd,J=1, 8Hz), 8.66 (1H,d,J=8Hz), 8.75
(1H,br s)Production Example 28 The following compounds (1) to (19) were produced in the same manner as in Production Example 1- (5). (1) 3-isobutyryl-2-propylindole-7-
Carboxylic acid methyl ester NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.27 (6H, d, J = 7
Hz), 1.82 (2H, m), 3.26 (2H, m), 3.47 (1H, m), 3.99 (3
H, s), 7.28 (1H, t, J = 8Hz), 7.85 (1H, d, J = 8Hz), 8.18 (1
H, s) (2) 3-isobutyryl-2-propylindole-5
Carboxylic acid methyl ester NMR (CDCl3 , δ): 1.04 (3H, t, J = 8Hz), 1.28 (6H, d, J = 8
Hz), 1.78 (2H, sextet, J = 8Hz), 3.15 (2H, t, J = 8Hz), 3.
56 (1H, septet, J = 8Hz), 3.96 (3H, s), 7.37 (1H, d, J = 1H
z), 7.93 (1H, dd, J = 1,8Hz), 8.66 (1H, d, J = 8Hz), 8.75
(1H, br s)
【０１５３】(3) ３−（３−メトキシカルボニルプロパ
ノイル）インドール−６−カルボン酸メチルエステル NMR (DMSO-d ,δ) : 2.65 (2H,t,J=7Hz), 3.22 (2H,t,J
=7Hz), 3.59 (3H,s),3.87 (3H,s), 7.80 (1H,d,J=8Hz),
8.10 (1H,s), 8.23 (1H,d,J=8Hz),8.59 (1H,s) (4) ３−アセチル−２−メチルインドール−６−カルボ
ン酸メチルエステル NMR (CDCl3,δ) : 2.54 (3H,s), 2.73 (3H,s), 3.86 (3
H,s), 7.76 (1H,d,J=8Hz), 7.97 (1H,s), 8.12 (1H,d,J
=8Hz)(3) 3- (3-methoxycarbonylpropanoyl) indole-6-carboxylic acid methyl ester NMR (DMSO-d, δ): 2.65 (2H, t, J = 7Hz), 3.22 (2H, t, J
= 7Hz), 3.59 (3H, s), 3.87 (3H, s), 7.80 (1H, d, J = 8Hz),
8.10 (1H, s), 8.23 (1H, d, J = 8Hz), 8.59 (1H, s) (4) 3- acetyl-2-methylindole-6-carboxylic acid methyl ester NMR (CDCl3, δ): 2.54 (3H, s), 2.73 (3H, s), 3.86 (3
H, s), 7.76 (1H, d, J = 8Hz), 7.97 (1H, s), 8.12 (1H, d, J
= 8Hz)
【０１５４】(5) ２−メチル−３−プロピオニルインド
ール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.12 (3H,t,J=7Hz), 2.72 (3H,s),
2.92 (2H,q,J=7Hz),3.86 (3H,s), 7.75 (1H,d,J=8Hz),
7.96 (1H,s), 8.11 (1H,d,J=8Hz) (6) ３−（３,３−ジメチルブタノイル）インドール−
６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.11 (9H,m), 2.33 (2H,s), 3.94 (3
H,s), 7.92-8.0 (2H,m), 8.19 (1H,s), 8.52 (1H,d,J=8
Hz), 8.90 (1H,br s)(5) 2-methyl-3-propionylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.12 (3H, t, J = 7 Hz), 2.72 (3H, s),
2.92 (2H, q, J = 7Hz), 3.86 (3H, s), 7.75 (1H, d, J = 8Hz),
7.96 (1H, s), 8.11 (1H, d, J = 8Hz) (6) 3- (3,3-dimethylbutanoyl) indole-
6-Carboxylic acid methyl ester NMR (CDCl3 , δ): 1.11 (9H, m), 2.33 (2H, s), 3.94 (3
H, s), 7.92-8.0 (2H, m), 8.19 (1H, s), 8.52 (1H, d, J = 8
Hz), 8.90 (1H, br s)
【０１５５】(7) ３−イソブチリル−２−プロピルイン
ドール−６−イル酢酸エチルエステル IR (ニート) : 3300, 1740, 1625 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.25 (6H,d,J=7
Hz), 1.26 (3H,t,J=7Hz), 1.77 (2H,sextet,J=7Hz), 3.
12 (2H,t,J=7Hz), 3.41-3.55 (1H,m), 3.72 (2H,s), 4.
16 (2H,q,J=7Hz), 7.17 (1H,d,J=7.5Hz), 7.30(1H,s),
7.82 (1H,d,J=7.5Hz), 8.40 (1H,br s) MASS (m/z) : 316 (M++1), 74 (bp) (8) ３−イソブチリル−２−プロピルインドール−６−
イル酢酸メチルエステル IR (ニート) : 3290, 1730, 1625 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.26 (6H,d,J=7
Hz), 1.76 (2H,sextet,J=7Hz), 3.12 (2H,t,J=7Hz), 3.
41-3.54 (1H,m), 3.71 (2H,s),3.75 (3H,s), 7.16 (1H,
d,J=7.5Hz), 7.30 (1H,s), 7.83 (1H,d,J=7.5Hz), 8.40
(1H,br s) MASS (m/z) : 302 (M++1, bp)(7) 3-isobutyryl-2-propylindol-6-ylacetic acid ethyl ester IR (neat): 3300, 1740, 1625 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.25 (6H, d, J = 7
Hz), 1.26 (3H, t, J = 7Hz), 1.77 (2H, sextet, J = 7Hz), 3.
12 (2H, t, J = 7Hz), 3.41-3.55 (1H, m), 3.72 (2H, s), 4.
16 (2H, q, J = 7Hz), 7.17 (1H, d, J = 7.5Hz), 7.30 (1H, s),
7.82 (1H, d, J = 7.5Hz), 8.40 (1H, brs) MASS (m / z): 316 (M++ 1), 74 (bp) (8) 3-isobutyryl-2-propylindole 6-
Methyl ylacetate IR (neat): 3290, 1730, 1625 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.26 (6H, d, J = 7
Hz), 1.76 (2H, sextet, J = 7Hz), 3.12 (2H, t, J = 7Hz), 3.
41-3.54 (1H, m), 3.71 (2H, s), 3.75 (3H, s), 7.16 (1H,
d, J = 7.5Hz), 7.30 (1H, s), 7.83 (1H, d, J = 7.5Hz), 8.40
(1H, br s) MASS (m / z): 302 (M+ +1, bp)
【０１５６】(9) ２−アセチル−３−メチルインドール
−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 2.66 (3H,s), 2.67 (3H,s), 3.94 (3
H,s), 7.72 (1H,d,J=8Hz), 7.81 (1H,d,J=8Hz), 8.11
(1H,s), 9.09 (1H,br s) (10) ３−プロピオニルインドール−６−カルボン酸メ
チルエステル NMR (CDCl3,δ) : 1.12 (3H,t,J=7Hz), 2.89 (2H,q,J=7
Hz), 3.87 (3H,s),7.79 (1H,d,J=8Hz), 8.11 (1H,s),
8.28 (1H,d,J=8Hz), 8.53 (1H,s)(9) 2-acetyl-3-methylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.66 (3H, s), 2.67 (3H, s), 3.94 (3
H, s), 7.72 (1H, d, J = 8Hz), 7.81 (1H, d, J = 8Hz), 8.11
(1H, s), 9.09 ( 1H, br s) (10) 3- propionyl-indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.12 (3H, t, J = 7Hz), 2.89 (2H, q, J = 7
Hz), 3.87 (3H, s), 7.79 (1H, d, J = 8Hz), 8.11 (1H, s),
8.28 (1H, d, J = 8Hz), 8.53 (1H, s)
【０１５７】(11) ２−プロピオニル−３−プロピルイ
ンドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.06 (3H,t,J=7Hz), 1.29 (3H,t,J=7
Hz), 1.74 (2H,m),2.95-3.13 (4H,m), 3.94 (3H,s), 7.
72 (1H,d,J=8Hz), 7.79 (1H,d,J=8Hz), 8.12 (1H,s),
9.11 (1H,br s) (12) ２−イソブチリル−３−プロピルインドール−６
−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.29 (6H,t,J=7
Hz), 1.76 (2H,m),3.09 (2H,m), 3.44 (1H,m), 3.94 (3
H,s), 7.71 (1H,d,J=8Hz), 7.79(1H,d,J=8Hz), 8.12 (1
H,s), 9.12 (1H,br s)(11) 2-propionyl-3-propylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.06 (3H, t, J = 7 Hz), 1.29 (3H, t, J = 7)
Hz), 1.74 (2H, m), 2.95-3.13 (4H, m), 3.94 (3H, s), 7.
72 (1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz), 8.12 (1H, s),
9.11 (1H, brs) (12) 2-isobutyryl-3-propylindole-6
- carboxylic acid methyl esterNMR (CDCl 3, δ): 1.04 (3H, t, J = 7Hz), 1.29 (6H, t, J = 7
Hz), 1.76 (2H, m), 3.09 (2H, m), 3.44 (1H, m), 3.94 (3
H, s), 7.71 (1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz), 8.12 (1
H, s), 9.12 (1H, br s)
【０１５８】(13) ３−シクロプロパンカルボニル−２
−プロピルインドール−６−カルボン酸メチルエステル mp : 152.5−154℃ IR (KBr) : 3371, 1687, 1623, 1458 cm-1 NMR (CDCl3,δ) : 1.00-1.09 (2H,m), 1.02 (3H,t,J=7H
z), 1.28-1.32 (2H,m), 1.82 (2H,sextet,J=7Hz), 2.56
-2.65 (1H,m), 3.15 (2H,t,J=7Hz),3.96 (3H,s), 8.00
(2H,AB,J=8, 8Hz), 8.15 (1H,s), 8.89 (1H,br s)MASS
(m/z) : 286 (M++1, bp) (14) ３−シクロブタンカルボニル−２−プロピルイン
ドール−６−カルボン酸メチルエステル mp : 159−160℃ IR (KBr) : 1692, 1645, 1623 cm-1 NMR (CDCl3,δ) : 1.06 (3H,t,J=7Hz), 1.83 (2H,sexte
t,J=7Hz), 1.93-2.13(2H,m), 2.30-2.51 (4H,m), 3.20
(2H,t,J=7Hz), 3.95 (3H,s), 3.99(1H,quintet,J=7Hz),
7.93 (2H,s), 8.15 (1H,s), 9.08 (1H,br s) MASS (m/z) : 300 (M++1), 74 (bp)(13) 3-cyclopropanecarbonyl-2
-Propylindole-6-carboxylic acid methyl ester mp: 152.5-154 ° C IR (KBr): 3371, 1687, 1623, 1458 cm-1 NMR (CDCl3 , δ): 1.00-1.09 (2H, m), 1.02 ( 3H, t, J = 7H
z), 1.28-1.32 (2H, m), 1.82 (2H, sextet, J = 7Hz), 2.56
-2.65 (1H, m), 3.15 (2H, t, J = 7Hz), 3.96 (3H, s), 8.00
(2H, AB, J = 8,8Hz), 8.15 (1H, s), 8.89 (1H, br s) MASS
(m / z): 286 (M++ 1, bp) (14) 3-cyclobutanecarbonyl-2-propylindole-6-carboxylic acid methyl ester mp: 159-160 ° C IR (KBr): 1692, 1645, 1623 cm-1 NMR (CDCl3 , δ): 1.06 (3H, t, J = 7Hz), 1.83 (2H, sexte
(t, J = 7Hz), 1.93-2.13 (2H, m), 2.30-2.51 (4H, m), 3.20
(2H, t, J = 7Hz), 3.95 (3H, s), 3.99 (1H, quintet, J = 7Hz),
7.93 (2H, s), 8.15 (1H, s), 9.08 (1H, br s) MASS (m / z): 300 (M+ +1), 74 (bp)
【０１５９】(15) ３−シクロペンタンカルボニル−２
−プロピルインドール−６−カルボン酸メチルエステル mp : 137−139℃ IR (KBr) : 1692, 1647, 1624 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.64-1.82 (6H,
m), 1.94-2.05 (4H,m), 3.17 (2H,t,J=7Hz), 3.72 (1H,
quintet,J=7Hz), 3.95 (3H,s), 7.93(2H,ABX,J=8, 8, 1
Hz), 8.15 (1H,d,J=1Hz), 9.19 (1H,s) MASS (m/z) : 314 (M++1, bp) (16) ３−シクロヘキサンカルボニル−２−プロピルイ
ンドール−６−カルボン酸メチルエステル mp : 136−137℃ IR (KBr) : 1691, 1651, 1487, 1435 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.25-2.04 (12
H,m), 3.14-3.25 (1H,m), 3.18 (2H,t,J=7Hz), 3.97 (3
H,s), 7.90 (2H,q,J=7.5Hz), 8.17(1H,s), 9.16 (1H,br
s) MASS (m/z) : 328 (M++1), 74 (bp)(15) 3-cyclopentanecarbonyl-2
-Propylindole-6-carboxylic acid methyl ester mp: 137-139 ° C IR (KBr): 1692, 1647, 1624 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.64- 1.82 (6H,
m), 1.94-2.05 (4H, m), 3.17 (2H, t, J = 7Hz), 3.72 (1H,
quintet, J = 7Hz), 3.95 (3H, s), 7.93 (2H, ABX, J = 8,8,1
Hz), 8.15 (1H, d, J = 1Hz), 9.19 (1H, s) MASS (m / z): 314 (M++ 1, bp) (16) 3-cyclohexanecarbonyl-2-propylindole-6 -Carboxylic acid methyl ester mp: 136-137 ° C IR (KBr): 1691, 1651, 1487, 1435 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.25-2.04 (12
H, m), 3.14-3.25 (1H, m), 3.18 (2H, t, J = 7Hz), 3.97 (3
H, s), 7.90 (2H, q, J = 7.5Hz), 8.17 (1H, s), 9.16 (1H, br
s) MASS (m / z): 328 (M+ +1), 74 (bp)
【０１６０】(17) ３−（３−メチル−２−ブテノイ
ル）−２−プロピルインドール−６−カルボン酸メチル
エステル mp : 146−147℃ IR (KBr) : 1715, 1464, 1433, 1220 cm-1 NMR (CDCl3,δ) : 1.05 (3H,t,J=7Hz), 1.82 (2H,sexte
t,J=7Hz), 2.05 (3H,s), 2.20 (3H,s), 3.18 (2H,t,J=7
Hz), 3.94 (3H,s), 6.63 (1H,s),7.95 (2H,AB,J=7.5,
7.5Hz), 8.11 (1H,s), 8.88 (1H,br s) MASS (m/z) : 300 (M++1), 74 (bp) (18) ３−クロトノイル−２−プロピルインドール−６
−カルボン酸メチルエステル mp : 153−154℃ IR (KBr) : 1715, 1650, 1583, 1567, 1459, 1432 cm-1 NMR (CDCl3,δ) : 1.05 (3H,t,J=7Hz), 1.83 (2H,sexte
t,J=7Hz), 2.04 (3H,dd,J=7, 1Hz), 3.15 (2H,t,J=7H
z), 3.96 (3H,s), 6.89 (1H,dd,J=15,1Hz), 7.04 (1H,d
d,J=15, 7Hz), 7.94 (2H,dq,J=7, 1Hz), 8.12 (1H,s),
8.99 (1H,br s) MASS (m/z) : 286 (M++1)(17) 3- (3-methyl-2-butenoyl) -2-propylindole-6-carboxylic acid methyl ester mp: 146-147 ° C IR (KBr): 1715, 1464, 1433, 1220 cm-1 NMR (CDCl3 , δ): 1.05 (3H, t, J = 7Hz), 1.82 (2H, sexte
t, J = 7Hz), 2.05 (3H, s), 2.20 (3H, s), 3.18 (2H, t, J = 7
Hz), 3.94 (3H, s), 6.63 (1H, s), 7.95 (2H, AB, J = 7.5,
7.5Hz), 8.11 (1H, s), 8.88 (1H, brs) MASS (m / z): 300 (M++ 1), 74 (bp) (18) 3-crotonoyl-2-propylindole-6
-Carboxylic acid methyl ester mp: 153-154 ° C IR (KBr): 1715, 1650, 1583, 1567, 1459, 1432 cm-1 NMR (CDCl3 , δ): 1.05 (3H, t, J = 7Hz), 1.83 (2H, sexte
t, J = 7Hz), 2.04 (3H, dd, J = 7,1Hz), 3.15 (2H, t, J = 7H
z), 3.96 (3H, s), 6.89 (1H, dd, J = 15,1Hz), 7.04 (1H, d
d, J = 15,7Hz), 7.94 (2H, dq, J = 7,1Hz), 8.12 (1H, s),
8.99 (1H, br s) MASS (m / z): 286 (M+ +1)
【０１６１】(19) ３−アセチル−６−クロロインドー
ル NMR (CDCl3,δ) : 2.44 (3H,s), 7.19 (1H,d,J=8Hz),
7.51 (1H,s), 8.14(1H,d,J=8Hz), 8.35 (1H,s)(19) 3-acetyl-6-chloroindole NMR (CDCl3 , δ): 2.44 (3H, s), 7.19 (1H, d, J = 8 Hz),
7.51 (1H, s), 8.14 (1H, d, J = 8Hz), 8.35 (1H, s)
【０１６２】製造例29 製造例６−(2)と同様にして、次の(1)〜(3)に記載の化
合物を製造した。 (1) ３−（３−メトキシカルボニルプロピル）インドー
ル−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 2.04 (2H,m), 2.37 (2H,t,J=7Hz),
2.81 (2H,t,J=7Hz),3.64 (3H,s), 3.93 (3H,s), 7.16
(1H,s), 7.61 (1H,d,J=8Hz), 7.79(1H,d,J=8Hz), 8.10
(1H,s), 8.22 (1H,br s) (2) ３−メチルインドール−６−カルボン酸メチルエス
テル NMR (CDCl3,δ) : 2.33 (3H,s), 3.93 (3H,s), 7.12 (1
H,s), 7.59 (1H,d,J=8Hz), 7.80 (1H,d,J=8Hz), 8.09
(1H,s), 8.10 (1H,br s)Production Example 29 The following compounds (1) to (3) were produced in the same manner as in Production Example 6- (2). (1) 3- (3-methoxycarbonylpropyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.04 (2H, m), 2.37 (2H, t, J = 7Hz),
2.81 (2H, t, J = 7Hz), 3.64 (3H, s), 3.93 (3H, s), 7.16
(1H, s), 7.61 (1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz), 8.10
(1H, s), 8.22 ( 1H, br s) (2) 3- methyl-indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 2.33 (3H, s), 3.93 (3H, s), 7.12 (1
H, s), 7.59 (1H, d, J = 8Hz), 7.80 (1H, d, J = 8Hz), 8.09
(1H, s), 8.10 (1H, br s)
【０１６３】(3) ３−プロピルインドール−６−カルボ
ン酸メチルエステル NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.74 (2H,m),
2.73 (2H,t,J=7Hz),3.93 (3H,s), 7.14 (1H,d,J=1Hz),
7.60 (1H,d,J=8Hz), 7.79 (1H,d,J=8Hz), 8.10 (1H,s),
8.18 (1H,br s)(3) 3-propylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.00 (3H, t, J = 7 Hz), 1.74 (2H, m),
2.73 (2H, t, J = 7Hz), 3.93 (3H, s), 7.14 (1H, d, J = 1Hz),
7.60 (1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz), 8.10 (1H, s),
8.18 (1H, br s)
【０１６４】製造例30 ３−（３−メトキシカルボニルプロピル）インドール−
６−カルボン酸メチルエステル（656mg）のメタノール
（24ml）溶液に、１Ｎ水酸化ナトリウム水溶液（2.46m
l）を加え、混合物を20℃で２日間撹拌した。生じた混
合物を減圧下で蒸発させ、残留物を１Ｎ塩酸（2.6ml）
で酸性化し、酢酸エチルで抽出した。有機層を食塩水で
洗い、硫酸ナトリウムで乾燥し、減圧下で蒸発させた。
残留物をエーテルを用いて粉末化して、３−（３−カル
ボキシプロピル）インドール−６−カルボン酸メチルエ
ステル（486mg）を固体として得た。 NMR (CDCl3,δ) : 2.03 (2H,m), 2.37 (2H,m), 2.80 (2
H,m), 3.93 (3H,s),7.17 (1H,s), 7.59 (1H,d,J=8Hz),
7.74 (1H,d,J=8Hz), 8.09 (1H,s)Production Example 30 3- (3-methoxycarbonylpropyl) indole-
To a solution of 6-carboxylic acid methyl ester (656 mg) in methanol (24 ml) was added a 1N aqueous sodium hydroxide solution (2.46 m
l) was added and the mixture was stirred at 20 ° C. for 2 days. The resulting mixture was evaporated under reduced pressure and the residue was washed with 1N hydrochloric acid (2.6 ml)
And extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure.
The residue was triturated with ether to give 3- (3-carboxypropyl) indole-6-carboxylic acid methyl ester (486 mg) as a solid. NMR (CDCl3 , δ): 2.03 (2H, m), 2.37 (2H, m), 2.80 (2
H, m), 3.93 (3H, s), 7.17 (1H, s), 7.59 (1H, d, J = 8Hz),
7.74 (1H, d, J = 8Hz), 8.09 (1H, s)
【０１６５】製造例31 ３−（３−カルボキシプロピル）インドール−６−カル
ボン酸メチルエステル（173mg）、トリフェニルホスフ
ィン（191mg）および四塩化炭素（1.0ml）の１,２−ジ
クロロエタン（10ml）中混合物を、80℃で２時間加熱し
た。生じた混合物をクロロホルムで希釈し、水、炭酸ナ
トリウム水溶液および食塩水で洗った。有機層を硫酸ナ
トリウムで乾燥し、減圧下で蒸発させた。残留物を、ヘ
キサン−酢酸エチル（４：１）混合物を用いてのシリカ
ゲル薄層クロマトグラフィーにより精製し、ヘキサン−
酢酸エチル混合物から再結晶して、８−オキソ−５,６,
７,８−テトラヒドロカルバゾール−２−カルボン酸メ
チルエステル（72.2mg）を無色結晶として得た。 NMR (CDCl3,δ) : 2.29 (2H,m), 2.69 (2H,t,J=7Hz),
3.03 (2H,t,J=7Hz),3.94 (3H,s), 7.69 (1H,d,J=8Hz),
7.82 (1H,d,J=8Hz), 8.16 (1H,s),8.95 (1H,br s)Production Example 31 3- (3-Carboxypropyl) indole-6-carboxylic acid methyl ester (173 mg), triphenylphosphine (191 mg) and carbon tetrachloride (1.0 ml) in 1,2-dichloroethane (10 ml) The mixture was heated at 80 C for 2 hours. The resulting mixture was diluted with chloroform and washed with water, aqueous sodium carbonate and brine. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by silica gel thin layer chromatography using a hexane-ethyl acetate (4: 1) mixture,
Recrystallization from the ethyl acetate mixture gave 8-oxo-5,6,
7,8-Tetrahydrocarbazole-2-carboxylic acid methyl ester (72.2 mg) was obtained as colorless crystals. NMR (CDCl3 , δ): 2.29 (2H, m), 2.69 (2H, t, J = 7Hz),
3.03 (2H, t, J = 7Hz), 3.94 (3H, s), 7.69 (1H, d, J = 8Hz),
7.82 (1H, d, J = 8Hz), 8.16 (1H, s), 8.95 (1H, br s)
【０１６６】製造例32 ジャーナル・オブ・メディシナル・ケミストリー（J. M
ed. Chem.）35巻2419頁（1992年）に記載されているブ
ラウン（Brown）らの方法により製造した(Ｅ)−４−
［２−（ジメチルアミノ）ビニル］−３−ニトロ安息香
酸メチルエステル（500mg）とピリジン（0.16ml）との
テトラヒドロフラン（３ml）中混合物に、20℃で撹拌
下、塩化ブチリル（0.21ml）を加えた。反応混合物を40
℃で24時間、50℃で４時間撹拌した。20℃まで冷却後、
反応混合物を水で希釈し、酢酸エチルで抽出した。有機
層を水および食塩水で洗い、硫酸マグネシウムで乾燥
し、減圧下で蒸発させた。残留物をシリカゲルクロマト
グラフィーに付し、酢酸エチル−ヘキサン（１：１）混
合物で溶出して、４−（１−ジメチルアミノメチレン−
２−オキソペンチル）−３−ニトロ安息香酸メチルエス
テル（426mg）を無色無定形物として得た。 NMR (CDCl3,δ) : 0.89 (3H,t,J=7Hz), 1.52-1.65 (2H,
m), 2.30 (2H,t,J=7Hz), 2.78 (6H,s), 3.99 (3H,s),
7.34 (1H,d,J=7.5Hz), 7.56 (1H,s), 8.18 (1H,dd,J=7.
5, 1Hz), 8.51 (1H,d,J=1Hz) MASS (m/z) : 321 (M++1)Production Example 32 Journal of Medicinal Chemistry (J.M.
ed. Chem.) 35, 2419 (1992), prepared by the method of Brown et al.
To a mixture of [2- (dimethylamino) vinyl] -3-nitrobenzoic acid methyl ester (500 mg) and pyridine (0.16 ml) in tetrahydrofuran (3 ml) was added butyryl chloride (0.21 ml) with stirring at 20 ° C. Was. 40 reaction mixture
The mixture was stirred for 24 hours at 50 ° C and 4 hours at 50 ° C. After cooling to 20 ° C,
The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate-hexane (1: 1) to give 4- (1-dimethylaminomethylene-
Methyl 2-oxopentyl) -3-nitrobenzoate (426 mg) was obtained as a colorless amorphous. NMR (CDCl3 , δ): 0.89 (3H, t, J = 7Hz), 1.52-1.65 (2H,
m), 2.30 (2H, t, J = 7Hz), 2.78 (6H, s), 3.99 (3H, s),
7.34 (1H, d, J = 7.5Hz), 7.56 (1H, s), 8.18 (1H, dd, J = 7.
5, 1Hz), 8.51 (1H, d, J = 1Hz) MASS (m / z): 321 (M+ +1)
【０１６７】製造例33 ４−（１−ジメチルアミノメチレン−２−オキソペンチ
ル）−３−ニトロ安息香酸メチルエステル（172mg）の
ジオキサン（９ml）溶液を、４日間還流下に加熱した。
生じた混合物を減圧下で蒸発させ、残留物を、ヘキサン
−酢酸エチル（２：１）混合物を用いての薄層クロマト
グラフィーにより精製して、３−ニトロ−４−（２−オ
キソペンチル）安息香酸メチルエステル（127mg）を得
た。 NMR (CDCl3,δ) : 0.97 (3H,t,J=7Hz), 1.69 (2H,m),
2.60 (2H,t,J=7Hz),3.95 (3H,s), 4.16 (2H,s), 7.36
(1H,d,J=8Hz), 8.22 (1H,d,J=8Hz),8.73 (1H,s)Production Example 33 A solution of methyl 4- (1-dimethylaminomethylene-2-oxopentyl) -3-nitrobenzoate (172 mg) in dioxane (9 ml) was heated under reflux for 4 days.
The resulting mixture was evaporated under reduced pressure and the residue was purified by thin layer chromatography using a hexane-ethyl acetate (2: 1) mixture to give 3-nitro-4- (2-oxopentyl) benzoic acid. The acid methyl ester (127 mg) was obtained. NMR (CDCl3 , δ): 0.97 (3H, t, J = 7Hz), 1.69 (2H, m),
2.60 (2H, t, J = 7Hz), 3.95 (3H, s), 4.16 (2H, s), 7.36
(1H, d, J = 8Hz), 8.22 (1H, d, J = 8Hz), 8.73 (1H, s)
【０１６８】製造例34 ３−ニトロ−４−（２−オキソペンチル）安息香酸メチ
ルエステル（114mg）のテトラヒドロフラン（1.5ml）−
エタノール（1.5ml）−水（2.1ml）混合物溶液に、亜ジ
チオン酸ナトリウム（3.0ｇ）を加え、混合物を30分間
還流下に撹拌した。生じた混合物を減圧下で蒸発させ、
残留物を酢酸エチルで希釈した。有機層を水および食塩
水で洗い、硫酸ナトリウムで乾燥し、減圧下で蒸発させ
た。残留物を、ヘキサン−酢酸エチル（２：１）混合物
を用いての薄層クロマトグラフィーにより精製して、２
−プロピルインドール−６−カルボン酸メチルエステル
（54.6mg）を得た。Production Example 34 Methyl 3-nitro-4- (2-oxopentyl) benzoate (114 mg) in tetrahydrofuran (1.5 ml)
To a solution of a mixture of ethanol (1.5 ml) and water (2.1 ml) was added sodium dithionite (3.0 g), and the mixture was stirred under reflux for 30 minutes. The resulting mixture was evaporated under reduced pressure,
The residue was diluted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by thin-layer chromatography using a hexane-ethyl acetate (2: 1) mixture to give 2
-Propylindole-6-carboxylic acid methyl ester (54.6 mg) was obtained.
【０１６９】製造例35 ３−イソブチリル−２−プロピルインドール−６−カル
ボン酸（331mg）のテトラヒドロフラン（５ml）溶液
に、20℃で撹拌下、ベンジルアルコール（1.25ml）、ジ
シクロヘキシルカルボジイミド（303mg）および４−ジ
メチルアミノピリジン（20mg）を加えた。反応混合物を
20℃で８時間撹拌した。沈殿した尿素化合物を濾去し、
濾液を減圧下で蒸発させた。残留物を酢酸エチルで抽出
し、抽出液を水（２回）および食塩水で洗った。有機層
を硫酸ナトリウムで乾燥し、減圧下で蒸発させた。残留
物をシリカゲルクロマトグラフィーに付し、酢酸エチル
−ヘキサン（１：４）混合物で溶出し、得られた結晶を
酢酸エチル−ヘキサン混合物から再結晶して、３−イソ
ブチリル−２−プロピルインドール−６−カルボン酸ベ
ンジルエステル（215mg）を無色結晶として得た。 mp : 102−104℃ IR (KBr) : 1700, 1655 cm-1 NMR (CDCl3,δ) : 1.05 (3H,t,J=7Hz), 1.28 (6H,t,J=7
Hz), 1.73-1.87 (2H,m), 3.17 (2H,t,J=7Hz), 3.45-3.5
3 (1H,m), 5.40 (2H,s), 7.32-7.50(5H,m), 7.95 (2H,A
B,J=9, 8Hz), 8.14 (1H,s), 8.59 (1H,br s) MASS (m/z) : 364 (M++1), 76 (bp)Production Example 35 In a solution of 3-isobutyryl-2-propylindole-6-carboxylic acid (331 mg) in tetrahydrofuran (5 ml) at 20 ° C. with stirring, benzyl alcohol (1.25 ml), dicyclohexylcarbodiimide (303 mg) and 4 -Dimethylaminopyridine (20 mg) was added. The reaction mixture
Stirred at 20 ° C. for 8 hours. The precipitated urea compound is filtered off,
The filtrate was evaporated under reduced pressure. The residue was extracted with ethyl acetate, and the extract was washed with water (twice) and brine. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography, eluted with an ethyl acetate-hexane (1: 4) mixture, and the obtained crystals were recrystallized from an ethyl acetate-hexane mixture to give 3-isobutyryl-2-propylindole-6. -Carboxylic acid benzyl ester (215 mg) was obtained as colorless crystals. mp: 102-104 ° C IR (KBr): 1700, 1655 cm-1 NMR (CDCl3 , δ): 1.05 (3H, t, J = 7Hz), 1.28 (6H, t, J = 7
Hz), 1.73-1.87 (2H, m), 3.17 (2H, t, J = 7Hz), 3.45-3.5
3 (1H, m), 5.40 (2H, s), 7.32-7.50 (5H, m), 7.95 (2H, A
B, J = 9,8Hz), 8.14 (1H, s), 8.59 (1H, br s) MASS (m / z): 364 (M+ +1), 76 (bp)
【０１７０】製造例36 実施例32と同様にして、次の化合物を製造した。 ３−ホルミルインドール−６−カルボン酸メチルエステ
ル NMR (CDCl3,δ) : 3.88 (3H,s), 7.83 (1H,dd,J=1, 8H
z), 8.12 (1H,s),8.16 (1H,d,J=8Hz), 8.49 (1H,s), 1
2.45 (1H,br s)Production Example 36 The following compound was produced in the same manner as in Example 32. 3-formylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 3.88 (3H, s), 7.83 (1H, dd, J = 1,8H
z), 8.12 (1H, s), 8.16 (1H, d, J = 8Hz), 8.49 (1H, s), 1
2.45 (1H, br s)
【０１７１】製造例37 ３−イソブチリル−２−プロピルインドール−６−カル
ボン酸メチルエステル（201mg）の四塩化炭素（７ml）
溶液に、Ｎ−ブロモスクシンイミド（187mg）および２,
２’−アゾビス（４−メトキシ−２,４−ジメチルバレ
ロニトリル）（20mg）を加え、30分間還流下に加熱し
た。生じた混合物を濾過し、濾液を減圧下で蒸発させ
た。残留物を分取シリカゲル薄層クロマトグラフィーに
より精製した。ヘキサン−酢酸エチル（２：１）混合物
で溶出して、２−（１−ブロモプロピル）−３−イソブ
チリルインドール−６−カルボン酸メチルエステル（17
9mg）を得た。この化合物を精製せずに直ちに使用し
た。Preparation Example 37 3-Isobutyryl-2-propylindole-6-carboxylic acid methyl ester (201 mg) in carbon tetrachloride (7 ml)
To the solution was added N-bromosuccinimide (187 mg) and 2,2
2′-Azobis (4-methoxy-2,4-dimethylvaleronitrile) (20 mg) was added, and the mixture was heated under reflux for 30 minutes. The resulting mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography. Elution with a hexane-ethyl acetate (2: 1) mixture gave 2- (1-bromopropyl) -3-isobutyrylindole-6-carboxylic acid methyl ester (17.
9 mg). This compound was used immediately without purification.
【０１７２】製造例38 ２−（１−ブロモプロピル）−３−イソブチリルインド
ール−６−カルボン酸メチルエステル（179mg）の１,２
−ジクロロエタン（８ml）溶液に、Ｎ,Ｎ−ジイソプロ
ピルエチルアミン（0.24ml）を加え、40分間還流下に加
熱した。生じた混合物を減圧下で蒸発させ、つぎに、残
留物を酢酸エチルで希釈し、希塩酸、水および食塩水で
洗った。有機層を硫酸ナトリウムで乾燥し、減圧下で蒸
発させた。ジエチルエーテルを用いて粉末化して、３−
イソブチリル−２−（１−プロペニル）インドール−６
−カルボン酸メチルエステル（55.2mg）を得た。 NMR (CDCl3,δ) : 1.27 (6H,d,J=7Hz), 2.01 (3H,d,J=7
Hz), 3.47 (1H,m),3.93 (3H,s), 6.44 (1H,m), 7.32 (1
H,d,J=16Hz), 7.89 (1H,d,J=8Hz),7.94 (1H,d,J=8Hz),
8.11 (1H,s), 8.94 (1H,br s)Production Example 38 1,2-Methyl 2- (1-bromopropyl) -3-isobutyrylindole-6-carboxylate (179 mg)
To a solution of -dichloroethane (8 ml) was added N, N-diisopropylethylamine (0.24 ml), and the mixture was heated under reflux for 40 minutes. The resulting mixture was evaporated under reduced pressure, then the residue was diluted with ethyl acetate and washed with dilute hydrochloric acid, water and brine. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. Powdered with diethyl ether to give 3-
Isobutyryl-2- (1-propenyl) indole-6
-Methyl carboxylate (55.2 mg) was obtained. NMR (CDCl3 , δ): 1.27 (6H, d, J = 7Hz), 2.01 (3H, d, J = 7
Hz), 3.47 (1H, m), 3.93 (3H, s), 6.44 (1H, m), 7.32 (1
H, d, J = 16Hz), 7.89 (1H, d, J = 8Hz), 7.94 (1H, d, J = 8Hz),
8.11 (1H, s), 8.94 (1H, br s)
【０１７３】製造例39 ２−（１−ブロモプロピル）−３−イソブチリルインド
ール−６−カルボン酸メチルエステル（323mg）の酢酸
（３ml）溶液に、酢酸カリウム（345mg）を加え、混合
物を60℃で２時間撹拌する。生じた混合物を減圧下で蒸
発させ、つぎに、残留物を酢酸エチルで希釈し、水、炭
酸ナトリウム水溶液および食塩水で洗った。有機層を硫
酸ナトリウムで乾燥し、減圧下で蒸発させた。残留物を
分取シリカゲル薄層クロマトグラフィーに付し、ヘキサ
ン−酢酸エチル（２：１）混合物により溶出して、２−
（１−アセトキシプロピル）−３−イソブチリルインド
ール−６−カルボン酸メチルエステル（207mg）を得
た。 NMR (CDCl3,δ) : 0.99 (3H,t,J=7Hz), 1.23 (3H,d,J=7
Hz), 1.29 (3H,d,J=7Hz), 1.94 (1H,m), 2.08 (1H,m),
2.18 (3H,s), 3.52 (1H,m), 3.94(3H,s), 6.67 (1H,m),
7.88 (1H,d,J=8Hz), 7.94 (1H,d,J=8Hz), 8.18(1H,s),
9.09 (1H,br s)Production Example 39 To a solution of 2- (1-bromopropyl) -3-isobutyrylindole-6-carboxylic acid methyl ester (323 mg) in acetic acid (3 ml) was added potassium acetate (345 mg). Stir for 2 hours at ° C. The resulting mixture was evaporated under reduced pressure, then the residue was diluted with ethyl acetate and washed with water, aqueous sodium carbonate and brine. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residue was subjected to preparative silica gel thin layer chromatography, eluting with a hexane-ethyl acetate (2: 1) mixture to give 2-
(1-Acetoxypropyl) -3-isobutyrylindole-6-carboxylic acid methyl ester (207 mg) was obtained. NMR (CDCl3 , δ): 0.99 (3H, t, J = 7Hz), 1.23 (3H, d, J = 7
Hz), 1.29 (3H, d, J = 7Hz), 1.94 (1H, m), 2.08 (1H, m),
2.18 (3H, s), 3.52 (1H, m), 3.94 (3H, s), 6.67 (1H, m),
7.88 (1H, d, J = 8Hz), 7.94 (1H, d, J = 8Hz), 8.18 (1H, s),
9.09 (1H, br s)
【０１７４】製造例40 ２−プロピルインドール−６−カルボン酸メチルエステ
ル（10ｇ）、メトキシ酢酸（4.6ml）および四塩化炭素
（13.4ml）の１,２−ジクロロエタン（45ml）中混合物
に、還流下、トリフェニルホスフィン（16.7ｇ）の１,
２−ジクロロエタン（30ml）溶液を１時間かけて徐々に
加え、生じた混合物をさらに８時間還流下に加熱した。
溶媒を蒸発させたのち、残留物をシリカゲルクロマトグ
ラフィーに付し、ヘキサン−酢酸エチル（１：１）混合
物で溶出し、ジエチルエーテルを用いて粉末化して、３
−メトキシアセチル−２−プロピルインドール−６−カ
ルボン酸メチルエステル（8.11ｇ）を得た。Preparation 40 A mixture of methyl 2-propylindole-6-carboxylate (10 g), methoxyacetic acid (4.6 ml) and carbon tetrachloride (13.4 ml) in 1,2-dichloroethane (45 ml) was refluxed. , Triphenylphosphine (16.7g)
A solution of 2-dichloroethane (30 ml) was added slowly over 1 hour and the resulting mixture was heated at reflux for a further 8 hours.
After evaporation of the solvent, the residue was chromatographed on silica gel, eluted with a hexane-ethyl acetate (1: 1) mixture, triturated with diethyl ether and dried.
-Methoxyacetyl-2-propylindole-6-carboxylic acid methyl ester (8.11 g) was obtained.
【０１７５】製造例41 製造例15−(1)と同様にして、次の化合物を製造した。 ３−エトキシアセチル−２−プロピルインドール−６−
カルボン酸メチルエステル NMR (CDCl3,δ) : 1.05 (3H,t,J=7Hz), 1.32 (3H,t,J=7
Hz), 1.84 (2H,sextet,J=8Hz), 3.22 (2H,t,J=7Hz), 3.
74 (3H,q,J=7Hz), 3.97 (3H,s),4.75 (2H,s), 7.83 (1
H,d,J=8Hz), 7.94 (1H,d,J=8Hz), 8.15 (1H,s),9.27 (1
H,br s)Production Example 41 The following compound was produced in the same manner as in Production Example 15- (1). 3-ethoxyacetyl-2-propylindole-6
Carboxylic acid methyl ester NMR (CDCl3 , δ): 1.05 (3H, t, J = 7Hz), 1.32 (3H, t, J = 7
Hz), 1.84 (2H, sextet, J = 8Hz), 3.22 (2H, t, J = 7Hz), 3.
74 (3H, q, J = 7Hz), 3.97 (3H, s), 4.75 (2H, s), 7.83 (1
H, d, J = 8Hz), 7.94 (1H, d, J = 8Hz), 8.15 (1H, s), 9.27 (1
H, br s)
【０１７６】製造例42 ４−ヒドロキシフェニル酢酸メチルエステル（10.0ｇ）
の酢酸（55ml）溶液に、０℃で撹拌下、硝酸（22.1ml）
を加えた。反応混合物を０℃で２時間撹拌した。20℃ま
で温めたのち、反応混合物を水（200ml）で希釈し、沈
殿した結晶を集めた。結晶をクロロホルムに溶解させ、
溶液を水で洗い、硫酸マグネシウムで乾燥し、減圧下で
蒸発させた。残留物をクロロホルム−ヘキサン混合物か
ら再結晶して、４−ヒドロキシ−３−ニトロフェニル酢
酸メチルエステル（9.3ｇ）を黄色結晶として得た。 mp : 64−69℃ IR (KBr) : 1734, 1540, 1534, 1263, 1170 cm-1 NMR (CDCl3,δ) : 3.64 (2H,s), 3.73 (3H,s), 7.14 (1
H,d,J=8Hz), 7.52(1H,dd,J=8, 1Hz), 8.02 (1H,d,J=1H
z) MASS (m/z) : 210 (M+-1)Production Example 42 4-Hydroxyphenylacetic acid methyl ester (10.0 g)
Nitric acid (22.1 ml) in a solution of acetic acid (55 ml) at 0 ° C. with stirring.
Was added. The reaction mixture was stirred at 0 ° C. for 2 hours. After warming to 20 ° C., the reaction mixture was diluted with water (200 ml) and the precipitated crystals were collected. Dissolve the crystals in chloroform,
The solution was washed with water, dried over magnesium sulfate and evaporated under reduced pressure. The residue was recrystallized from a chloroform-hexane mixture to give 4-hydroxy-3-nitrophenylacetic acid methyl ester (9.3 g) as yellow crystals. mp: 64-69 ° C IR (KBr): 1734, 1540, 1534, 1263, 1170 cm-1 NMR (CDCl3 , δ): 3.64 (2H, s), 3.73 (3H, s), 7.14 (1
H, d, J = 8Hz), 7.52 (1H, dd, J = 8,1Hz), 8.02 (1H, d, J = 1H
z) MASS (m / z): 210 (M+ -1)
【０１７７】製造例43 ３−ニトロ−４−トリフルオロメタンスルホニルオキシ
フェニル酢酸メチルエステル（2.97ｇ）と濃塩酸（7.3m
l）とのメタノール（22ml）中混合物に、０℃で撹拌
下、鉄粉（2.5ｇ）を少量づつ加えた。反応混合物を20
℃で２時間撹拌し、つぎに、酢酸エチル−飽和炭酸ナト
リウム混合物中に注いだ。有機層を飽和炭酸ナトリウム
および食塩水で洗い、硫酸ナトリウムで乾燥し、減圧下
で蒸発させた。残留物をシリカゲルクロマトグラフィー
に付し、酢酸エチル−ヘキサン（１：４）混合物で溶出
して、３−アミノ−４−トリフルオロメタンスルホニル
オキシフェニル酢酸メチルエステル（2.34ｇ）を無色結
晶として得た。 mp : 66−69℃ NMR (CDCl3,δ) : 3.57 (2H,s), 3.71 (3H,s), 3.94 (2
H,s), 6.67 (1H,dd,J=7.5, 1Hz), 6.79 (1H,d,J=1Hz),
7.11 (1H,d,J=7.5Hz)Production Example 43 3-Nitro-4-trifluoromethanesulfonyloxyphenylacetic acid methyl ester (2.97 g) and concentrated hydrochloric acid (7.3 m
To a mixture of 1) and methanol (22 ml) at 0 ° C. with stirring, iron powder (2.5 g) was added in small portions. 20 reaction mixture
Stirred at C for 2 hours then poured into ethyl acetate-saturated sodium carbonate mixture. The organic layer was washed with saturated sodium carbonate and brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography, and eluted with a mixture of ethyl acetate-hexane (1: 4) to give methyl 3-amino-4-trifluoromethanesulfonyloxyphenylacetate (2.34 g) as colorless crystals. mp: 66-69 ° C NMR (CDCl3 , δ): 3.57 (2H, s), 3.71 (3H, s), 3.94 (2
H, s), 6.67 (1H, dd, J = 7.5,1Hz), 6.79 (1H, d, J = 1Hz),
7.11 (1H, d, J = 7.5Hz)
【０１７８】製造例44 １−アセチル−２−プロピルインドール−６−イル酢酸
メチルエステルから、製造例26と同様にして、次の化合
物を製造した。 ２−プロピルインドール−６−イル酢酸メチルエステル IR (ニート) : 3400, 1740 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.75 (2H,sexte
t,J=7Hz), 2.72 (2H,t,J=7Hz), 3.70 (3H,s), 3.72 (2
H,s), 6.22 (1H,s), 6.99 (1H,d,J=7.5Hz), 7.22 (1H,
s), 7.47 (1H,d,J=7.5Hz), 7.83 (1H,br s) MASS (m/z) : 232 (M++1), 74 (bp) ２−プロピルインドール−６−イル酢酸エチルエステル IR (ニート) : 3400, 1735 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.05 (3H,t,J=7
Hz), 1.74 (2H,sextet,J=7Hz), 2.72 (2H,t,J=7Hz), 3.
69 (3H,s), 4.13 (2H,q,J=7Hz),6.20 (1H,s), 6.99 (1
H,d,J=7.5Hz), 7.23 (1H,s), 7.46 (1H,d,J=7.5Hz), 7.
83 (1H,br s) MASS (m/z) : 346 (M++1), 74 (bp) ２−プロピルインドール−６−イル酢酸 mp : 85−87℃ IR (KBr) : 3381, 1701, 1691 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.73 (2H,sexte
t,J=7Hz), 2.72 (2H,t,J=7Hz), 3.73 (2H,s), 6.21 (1
H,s), 6.98 (1H,d,J=7.5Hz), 7.21 (1H,s), 7.48 (1H,
d,J=7.5Hz), 7.83 (1H,br s) MASS (m/z) : 216 (M+-1, bp)Production Example 44 The following compound was produced from 1-acetyl-2-propylindol-6-ylacetic acid methyl ester in the same manner as in Production Example 26. 2-propylindol-6-ylacetic acid methyl ester IR (neat): 3400, 1740 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.75 (2H, sexte
t, J = 7Hz), 2.72 (2H, t, J = 7Hz), 3.70 (3H, s), 3.72 (2
H, s), 6.22 (1H, s), 6.99 (1H, d, J = 7.5Hz), 7.22 (1H,
s), 7.47 (1H, d, J = 7.5Hz), 7.83 (1H, brs) MASS (m / z): 232 (M++ 1), 74 (bp) 2-propylindol-6-ylacetic acid Ethyl ester IR (neat): 3400, 1735 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.05 (3H, t, J = 7
Hz), 1.74 (2H, sextet, J = 7Hz), 2.72 (2H, t, J = 7Hz), 3.
69 (3H, s), 4.13 (2H, q, J = 7Hz), 6.20 (1H, s), 6.99 (1
(H, d, J = 7.5Hz), 7.23 (1H, s), 7.46 (1H, d, J = 7.5Hz), 7.
83 (1H, brs) MASS (m / z): 346 (M+ +1), 74 (bp) 2-propylindol-6-ylacetic acid mp: 85-87 ° C IR (KBr): 3381, 1701, 1691 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.73 (2H, sexte
t, J = 7Hz), 2.72 (2H, t, J = 7Hz), 3.73 (2H, s), 6.21 (1
H, s), 6.98 (1H, d, J = 7.5Hz), 7.21 (1H, s), 7.48 (1H,
d, J = 7.5Hz), 7.83 (1H, br s) MASS (m / z): 216 (M+ -1, bp)
【０１７９】製造例45 ３−エチルインドール−６−カルボン酸メチルエステル
（138mg）のジクロロメタン（５ml）溶液に、撹拌下、
塩化スルフリル（0.066ml）を加え、混合物を20℃で１
時間撹拌した。生じた混合物を氷中に注ぎ、酢酸エチル
で抽出した。合わせた有機層を炭酸ナトリウム水溶液お
よび食塩水で洗い、つぎに硫酸ナトリウムで乾燥し、減
圧下で蒸発させた。残留物をシリカゲルクロマトグラフ
ィーに付し、ヘキサン−酢酸エチル（４：１）混合物で
溶出して、２−クロロ−３−エチルインドール−６−カ
ルボン酸メチル（58.2mg）を固体として得た。 NMR (CDCl3,δ) : 1.26 (3H,t,J=7Hz), 2.76 (2H,q,J=7
Hz), 3.92 (3H,s),7.54 (1H,d,J=8Hz), 7.82 (1H,d,J=8
Hz), 8.02 (1H,s), 8.19 (1H,br s)Production Example 45 A 3-ethylindole-6-carboxylic acid methyl ester (138 mg) solution in dichloromethane (5 ml) was stirred under stirring.
Sulfuryl chloride (0.066 ml) was added and the mixture was brought to
Stirred for hours. The resulting mixture was poured into ice and extracted with ethyl acetate. The combined organic layers were washed with aqueous sodium carbonate and brine, then dried over sodium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography and eluted with a hexane-ethyl acetate (4: 1) mixture to give methyl 2-chloro-3-ethylindole-6-carboxylate (58.2 mg) as a solid. NMR (CDCl3 , δ): 1.26 (3H, t, J = 7Hz), 2.76 (2H, q, J = 7
Hz), 3.92 (3H, s), 7.54 (1H, d, J = 8Hz), 7.82 (1H, d, J = 8
Hz), 8.02 (1H, s), 8.19 (1H, br s)
【０１８０】製造例46 ３−ホルミルインドール−６−カルボン酸メチルエステ
ル（368mg）の１,４−ジオキサン（10ml）溶液に、撹拌
下、アセチルメチレントリフェニルホスホラン（1.15
ｇ）を加え、混合物を12時間還流下に撹拌した。生じた
混合物を減圧下で蒸発させ、酢酸エチルに再溶解させ、
１Ｎ塩酸および食塩水で洗った。有機層を硫酸ナトリウ
ムで乾燥し、減圧下で蒸発させた。残留物をシリカゲル
クロマトグラフィーに付し、クロロホルム−酢酸エチル
（１：２）混合物で溶出して、３−（３−オキソ−１−
ブテニル）インドール−６−カルボン酸メチルエステル
（75mg）を固体として得た。 NMR (CDCl3,δ) : 2.39 (3H,s), 3.95 (3H,s), 6.79 (1
H,d,J=15Hz), 7.71(1H,s), 7.80 (1H,d,J=8Hz), 7.87-
7.96 (2H,m), 8.14 (1H,s)Production Example 46 To a solution of methyl 3-formylindole-6-carboxylate (368 mg) in 1,4-dioxane (10 ml) was stirred acetylmethylenetriphenylphosphorane (1.15).
g) was added and the mixture was stirred at reflux for 12 hours. The resulting mixture was evaporated under reduced pressure, redissolved in ethyl acetate,
Washed with 1N hydrochloric acid and brine. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with a mixture of chloroform-ethyl acetate (1: 2) to give 3- (3-oxo-1-
Butenyl) indole-6-carboxylic acid methyl ester (75 mg) was obtained as a solid. NMR (CDCl3 , δ): 2.39 (3H, s), 3.95 (3H, s), 6.79 (1
H, d, J = 15Hz), 7.71 (1H, s), 7.80 (1H, d, J = 8Hz), 7.87-
7.96 (2H, m), 8.14 (1H, s)
【０１８１】製造例47 製造例46と同様にして、次の化合物を製造した。 ３−（２−メトキシカルボニルエテニル）インドール−
６−カルボン酸メチルエステル NMR (DMSO-d ,δ) : 3.72 (3H,s), 4.87 (3H,s), 6.44
(1H,d,J=15Hz), 7.76(1H,d,J=8Hz), 7.89 (1H,d,J=15H
z), 7.98 (1H,d,J=8Hz), 8.10 (1H,s),8.20 (1H,s)Production Example 47 The following compound was produced in the same manner as in Production Example 46. 3- (2-methoxycarbonylethenyl) indole-
6-Carboxylic acid methyl ester NMR (DMSO-d, δ): 3.72 (3H, s), 4.87 (3H, s), 6.44
(1H, d, J = 15Hz), 7.76 (1H, d, J = 8Hz), 7.89 (1H, d, J = 15H)
z), 7.98 (1H, d, J = 8Hz), 8.10 (1H, s), 8.20 (1H, s)
【０１８２】製造例48 ３−（２−メトキシカルボニルエテニル）インドール−
６−カルボン酸メチルエステル（213mg）の１,４−ジオ
キサン（２ml）−メタノール（３ml）混合物溶液に、10
％パラジウム炭素（40mg）を加え、混合物を、水素雰囲
気下、20℃で6.5時間撹拌した。反応混合物をセライト
を通して濾過し、濾液を減圧下で蒸発させた。残留物を
ジイソプロピルエーテルを用いて粉末化して、３−（２
−メトキシカルボニルエチル）インドール−６−カルボ
ン酸メチルエステル（177mg）を得た。 NMR (CDCl3,δ) : 2.72 (2H,t,J=7Hz), 3.12 (2H,t,J=7
Hz), 3.68 (3H,s),3.94 (3H,s), 7.20 (1H,d,J=2Hz),
7.62 (1H,d,J=8Hz), 7.82 (1H,d,J=8Hz), 8.12 (1H,s),
8.21 (1H,br s)Production Example 48 3- (2-methoxycarbonylethenyl) indole-
To a solution of 6-carboxylic acid methyl ester (213 mg) in 1,4-dioxane (2 ml) -methanol (3 ml) was added 10
% Palladium on carbon (40 mg) was added and the mixture was stirred under a hydrogen atmosphere at 20 ° C. for 6.5 hours. The reaction mixture was filtered through celite and the filtrate was evaporated under reduced pressure. The residue was triturated with diisopropyl ether to give 3- (2
-Methoxycarbonylethyl) indole-6-carboxylic acid methyl ester (177 mg) was obtained. NMR (CDCl3 , δ): 2.72 (2H, t, J = 7Hz), 3.12 (2H, t, J = 7
Hz), 3.68 (3H, s), 3.94 (3H, s), 7.20 (1H, d, J = 2Hz),
7.62 (1H, d, J = 8Hz), 7.82 (1H, d, J = 8Hz), 8.12 (1H, s),
8.21 (1H, br s)
【０１８３】製造例49 製造例30と同様にして、次の化合物を製造した。 ３−（６−メトキシカルボニルインドール−３−イル）
プロピオン酸 NMR (CDCl3,δ) : 2.72 (2H,t,J=7Hz), 3.10 (2H,t,J=7
Hz), 3.94 (3H,s),7.19 (1H,s), 7.60 (1H,d,J=8Hz),
7.77 (1H,d,J=8Hz), 8.10 (1H,s)Production Example 49 The following compound was produced in the same manner as in Production Example 30. 3- (6-methoxycarbonylindol-3-yl)
Propionic acid NMR (CDCl3 , δ): 2.72 (2H, t, J = 7Hz), 3.10 (2H, t, J = 7
Hz), 3.94 (3H, s), 7.19 (1H, s), 7.60 (1H, d, J = 8Hz),
7.77 (1H, d, J = 8Hz), 8.10 (1H, s)
【０１８４】製造例50 製造例31と同様にして、次の化合物を製造した。 ３−オキソ−１,２,３,４−テトラヒドロシクロペンタ
［ｂ］インドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 3.05 (2H,m), 3.14 (2H,m), 3.97 (3
H,s), 7.76 (1H,d,J=8Hz), 7.85 (1H,d,J=8Hz), 8.21
(1H,s)Production Example 50 The following compound was produced in the same manner as in Production Example 31. 3-oxo-1,2,3,4-tetrahydrocyclopenta [b] indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 3.05 (2H, m), 3.14 (2H, m), 3.97 ( Three
H, s), 7.76 (1H, d, J = 8Hz), 7.85 (1H, d, J = 8Hz), 8.21
(1H, s)
【０１８５】製造例51 製造例８−(1)と同様にして、次の(1)〜(6)に記載の化
合物を製造した。 (1) ３−シクロプロパンカルボニル−２−プロピルイン
ドール−６−カルボン酸 mp : 250.5−251.5℃ (分解) IR (KBr) : 1685, 1600, 1463, 1424, 1300 cm-1 NMR (CDCl3-CD3OD,δ) : 1.00-1.09 (2H,m), 1.02 (3H,
t,J=7Hz), 1.25-1.29(2H,m), 1.81 (2H,sextet,J=7Hz),
2.59-2.69 (1H,m), 3.12 (2H,t,J=7Hz), 7.99 (2H,AB,
J=7.5, 7.5Hz), 8.09 (1H,s) MASS (m/z) : 270 (M+-1) (2) ３−シクロブタンカルボニル−２−プロピルインド
ール−６−カルボン酸 mp : 244−245℃ IR (KBr) : 1688, 1419, 1292 cm-1 NMR (CDCl3-CD3OD,δ) : 1.05 (3H,t,J=7Hz), 1.80 (2
H,sextet,J=7Hz),1.92-2.15 (2H,m), 2.29-2.49 (2H,
m), 4.01 (1H,quintet,J=7Hz), 7.90(2H,s), 8.08 (1H,
s) MASS (m/z) : 286 (M++1), 74 (bp)Production Example 51 The following compounds (1) to (6) were produced in the same manner as in Production Example 8- (1). (1) 3-cyclopropanecarbonyl-2-propylindole-6-carboxylic acid mp: 250.5-251.5 ° C (decomposition) IR (KBr): 1685, 1600, 1463, 1424, 1300 cm-1 NMR (CDCl3 -CD3 OD, δ): 1.00-1.09 (2H, m), 1.02 (3H,
t, J = 7Hz), 1.25-1.29 (2H, m), 1.81 (2H, sextet, J = 7Hz),
2.59-2.69 (1H, m), 3.12 (2H, t, J = 7Hz), 7.99 (2H, AB,
J = 7.5, 7.5Hz), 8.09 (1H, s) MASS (m / z): 270 (M+ -1) (2) 3-cyclobutanecarbonyl-2-propylindole-6-carboxylic acid mp: 244-245 ° C IR (KBr): 1688, 1419, 1292 cm-1 NMR (CDCl3 -CD3 OD, δ): 1.05 (3H, t, J = 7Hz), 1.80 (2
H, sextet, J = 7Hz), 1.92-2.15 (2H, m), 2.29-2.49 (2H,
m), 4.01 (1H, quintet, J = 7Hz), 7.90 (2H, s), 8.08 (1H,
s) MASS (m / z): 286 (M+ +1), 74 (bp)
【０１８６】(3) ３−シクロペンタンカルボニル−２−
プロピルインドール−６−カルボン酸 mp : 233−235℃ IR (KBr) : 1673, 1611, 1463, 1453 cm-1 NMR (CDCl3-CD3OD,δ) : 0.99 (3H,t,J=7Hz), 1.51-1.7
9 (6H,m), 1.89-1.97(4H,m), 3.10 (2H,t,J=7Hz), 3.70
(1H,quintet,J=7Hz), 7.85-7.94(2H,m), 8.05 (1H,s) MASS (m/z) : 298 (M+-1, bp) (4) ３−シクロヘキサンカルボニル−２−プロピルイン
ドール−６−カルボン酸 mp : 217−218℃ IR (KBr) : 1675, 1614, 1457 cm-1 NMR (CDCl3-CD3OD,δ) : 0.99 (3H,t,J=7Hz), 1.19-1.5
6 (6H,m), 1.74(2H,sextet,J=7Hz), 1.80-1.95 (4H,m),
3.08 (2H,t,J=7Hz), 3.09-3.20(1H,m), 7.80 (1H,d,J=
8Hz), 7.88 (1H,dd,J=8, 1Hz), 8.03 (1H,d,J=1Hz) MASS (m/z) : 312 (M+-1, bp)(3) 3-cyclopentanecarbonyl-2-
Propylindole-6-carboxylic acid mp: 233-235 ° C IR (KBr): 1673, 1611, 1463, 1453 cm-1 NMR (CDCl3 -CD3 OD, δ): 0.99 (3H, t, J = 7Hz) , 1.51-1.7
9 (6H, m), 1.89-1.97 (4H, m), 3.10 (2H, t, J = 7Hz), 3.70
(1H, quintet, J = 7Hz), 7.85-7.94 (2H, m), 8.05 (1H, s) MASS (m / z): 298 (M+ -1, bp) (4) 3-cyclohexanecarbonyl-2 -Propylindole-6-carboxylic acid mp: 217-218 ° C IR (KBr): 1675, 1614, 1457 cm-1 NMR (CDCl3 -CD3 OD, δ): 0.99 (3H, t, J = 7Hz), 1.19-1.5
6 (6H, m), 1.74 (2H, sextet, J = 7Hz), 1.80-1.95 (4H, m),
3.08 (2H, t, J = 7Hz), 3.09-3.20 (1H, m), 7.80 (1H, d, J =
8Hz), 7.88 (1H, dd, J = 8,1Hz), 8.03 (1H, d, J = 1Hz) MASS (m / z): 312 (M+ -1, bp)
【０１８７】(5) ３−（３−メチル−２−ブテノイル）
−２−プロピルインドール−６−カルボン酸 mp : 246−248℃ (分解) IR (KBr) : 1669, 1465, 1423 cm-1 NMR (DMSO-d6,δ) : 0.96 (3H,t,J=7Hz), 1.75 (2H,sex
tet,J=7Hz), 2.00(3H,s), 2.09 (3H,s), 3.08 (2H,t,J=
7Hz), 6.60 (1H,s), 7.73 (1H,d,J=7.5Hz), 7.95 (1H,
d,J=7.5Hz), 7.99 (1H,s) MASS (m/z) : 284 (M+-1, bp), 82 (bp)(5) 3- (3-methyl-2-butenoyl)
-2-Propylindole-6-carboxylic acid mp: 246-248 ° C (decomposition) IR (KBr): 1669, 1465, 1423 cm-1 NMR (DMSO-d6 , δ): 0.96 (3H, t, J = 7Hz), 1.75 (2H, sex
tet, J = 7Hz), 2.00 (3H, s), 2.09 (3H, s), 3.08 (2H, t, J =
7Hz), 6.60 (1H, s), 7.73 (1H, d, J = 7.5Hz), 7.95 (1H,
d, J = 7.5Hz), 7.99 (1H, s) MASS (m / z): 284 (M+ -1, bp), 82 (bp)
【０１８８】製造例52 実施例６と同様にして、次の(1)〜(6)に記載の化合物を
製造した。 (1) ３−シクロプロパンカルボニル−２−プロピルイン
ドール−６−カルボキサミド mp : 120−122℃ IR (KBr) : 1670, 1623, 1598, 1394 cm-1 NMR (DMSO-d6,δ) : 0.94 (3H,t,J=7Hz), 0.99-1.04 (4
H,m), 1.73 (2H,sextet,J=7Hz), 2.55-2.62 (1H,m), 3.
07 (2H,t,J=7Hz), 7.22 (1H,brs), 7.69 (1H,dd,J=7.5,
1Hz), 7.93 (1H,d,J=1Hz), 7.96 (1H,br s),8.00 (1H,
d,J=7.5Hz) MASS (m/z) : 269 (M+-1), 98 (bp) (2) ３−シクロブタンカルボニル−２−プロピルインド
ール−６−カルボキサミド mp : 253−255℃ IR (KBr) : 1675, 1624, 1605, 1456, 1397 cm-1 NMR (DMSO-d6,δ) : 0.97 (3H,t,J=7Hz), 1.66-1.89 (3
H,m), 1.97-2.09(1H,m), 2.23-2.30 (4H,m), 3.09 (2H,
t,J=7Hz), 3.99 (1H,quintet,J=7Hz), 7.24 (1H,br s),
7.69 (1H,d,J=7.5Hz), 7.86 (1H,d,J=7.5Hz),7.90 (1
H,s), 7.97 (1H,br s) MASS (m/z) : 285 (M++1), 85 (bp)Production Example 52 The following compounds (1) to (6) were produced in the same manner as in Example 6. (1) 3-cyclopropanecarbonyl-2-propylindole-6-carboxamide mp: 120-122 ° C IR (KBr): 1670, 1623, 1598, 1394 cm-1 NMR (DMSO-d6 , δ): 0.94 ( 3H, t, J = 7Hz), 0.99-1.04 (4
H, m), 1.73 (2H, sextet, J = 7Hz), 2.55-2.62 (1H, m), 3.
07 (2H, t, J = 7Hz), 7.22 (1H, brs), 7.69 (1H, dd, J = 7.5,
1Hz), 7.93 (1H, d, J = 1Hz), 7.96 (1H, br s), 8.00 (1H,
d, J = 7.5 Hz) MASS (m / z): 269 (M+ -1), 98 (bp) (2) 3-cyclobutanecarbonyl-2-propylindole-6-carboxamide mp: 253-255 ° C IR ( KBr): 1675, 1624, 1605, 1456, 1397 cm-1 NMR (DMSO-d6 , δ): 0.97 (3H, t, J = 7Hz), 1.66-1.89 (3
H, m), 1.97-2.09 (1H, m), 2.23-2.30 (4H, m), 3.09 (2H,
t, J = 7Hz), 3.99 (1H, quintet, J = 7Hz), 7.24 (1H, br s),
7.69 (1H, d, J = 7.5Hz), 7.86 (1H, d, J = 7.5Hz), 7.90 (1
H, s), 7.97 (1H, br s) MASS (m / z): 285 (M+ +1), 85 (bp)
【０１８９】(3) ３−シクロペンタンカルボニル−２−
プロピルインドール−６−カルボキサミド mp : 213−215℃ IR (KBr) : 1666, 1628, 1623, 1604 cm-1 NMR (CDCl3-CD3OD,δ) : 1.01 (3H,t,J=7Hz), 1.61-1.8
3 (6H,m), 1.90-1.98(4H,m), 3.13 (2H,t,J=7Hz), 3.69
(1H,quintet,J=7Hz), 7.52 (1H,dd,J=8, 1Hz), 7.91
(1H,d,J=1Hz), 7.96 (1H,d,J=8Hz) MASS (m/z) : 299 (M++1), 74 (bp) (4) ３−シクロヘキサンカルボニル−２−プロピルイン
ドール−６−カルボキサミド mp : 245−247℃ IR (KBr) : 1663, 1627, 1595, 1459, 1402 cm-1 NMR (DMSO-d6,δ) : 0.95 (3H,t,J=7Hz), 1.16-1.30 (1
H,m), 1.35-1.46(4H,m), 1.70 (2H,sextet,J=7Hz), 1.7
5-1.88 (5H,m), 3.05 (2H,t,J=7Hz), 3.10-3.17 (1H,
m), 7.25 (1H,br s), 7.70 (1H,dd,J=7.5,1Hz), 7.81
(1H,d,J=7.5Hz), 7.93 (1H,d,J=1Hz), 7.95 (1H,br s) MASS (m/z) : 313 (M++1), 85 (bp)(3) 3-cyclopentanecarbonyl-2-
Propylindole-6-carboxamide mp: 213-215 ° C IR (KBr): 1666, 1628, 1623, 1604 cm-1 NMR (CDCl3 -CD3 OD, δ): 1.01 (3H, t, J = 7Hz), 1.61-1.8
3 (6H, m), 1.90-1.98 (4H, m), 3.13 (2H, t, J = 7Hz), 3.69
(1H, quintet, J = 7Hz), 7.52 (1H, dd, J = 8,1Hz), 7.91
(1H, d, J = 1Hz), 7.96 (1H, d, J = 8Hz) MASS (m / z): 299 (M++ 1), 74 (bp) (4) 3-cyclohexanecarbonyl-2-propyl Indole-6-carboxamide mp: 245-247 ° C IR (KBr): 1663, 1627, 1595, 1459, 1402 cm-1 NMR (DMSO-d6 , δ): 0.95 (3H, t, J = 7Hz), 1.16 -1.30 (1
H, m), 1.35-1.46 (4H, m), 1.70 (2H, sextet, J = 7Hz), 1.7
5-1.88 (5H, m), 3.05 (2H, t, J = 7Hz), 3.10-3.17 (1H,
m), 7.25 (1H, br s), 7.70 (1H, dd, J = 7.5,1Hz), 7.81
(1H, d, J = 7.5Hz), 7.93 (1H, d, J = 1Hz), 7.95 (1H, br s) MASS (m / z): 313 (M+ +1), 85 (bp)
【０１９０】(5) ３−（３−メチル−２−ブテノイル）
−２−プロピルインドール−６−カルボキサミド mp : 179−181℃ IR (KBr) : 1669, 1648, 1591, 1458, 1394 cm-1 NMR (DMSO-d6,δ) : 0.95 (3H,t,J=7Hz), 1.72 (2H,sex
tet,J=7Hz), 1.99(3H,s), 2.05 (3H,s), 3.05 (2H,t,J=
7Hz), 6.59 (1H,s), 7.22 (1H,br s), 7.67 (1H,d,J=7.
5Hz), 7.88 (1H,d,J=7.5Hz), 7.90 (1H,s),7.92 (1H,br
s) MASS (m/z) : 285 (M++1), 85 (bp) (6) ３−（３−メトキシブタノイル）−２−プロピルイ
ンドール−６−カルボキサミド mp : 140−144℃ IR (KBr) : 1644, 1623, 1604, 1460, 1394 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.30 (3H,d,J=7
Hz), 1.80 (2H,sextet,J=7Hz), 2.98 (1H,dd,J=15, 7H
z), 3.17 (2H,t,J=7Hz), 3.39(1H,dd,J=15, 7Hz), 3.40
(3H,s), 7.10 (1H,sextet,J=7Hz), 7.55 (1H,dd,J=8,
1Hz), 8.02 (1H,d,J=8Hz), 8.10 (1H,d,J=1Hz), 9.60
(1H,br s) MASS (m/z) : 303 (M++1), 74 (bp)(5) 3- (3-methyl-2-butenoyl)
-2-Propylindole-6-carboxamide mp: 179-181 ° C IR (KBr): 1669, 1648, 1591, 1458, 1394 cm-1 NMR (DMSO-d6 , δ): 0.95 (3H, t, J = 7Hz), 1.72 (2H, sex
tet, J = 7Hz), 1.99 (3H, s), 2.05 (3H, s), 3.05 (2H, t, J =
7Hz), 6.59 (1H, s), 7.22 (1H, br s), 7.67 (1H, d, J = 7.
5Hz), 7.88 (1H, d, J = 7.5Hz), 7.90 (1H, s), 7.92 (1H, br
s) MASS (m / z): 285 (M++ 1), 85 (bp) (6) 3- (3-methoxybutanoyl) -2-propylindole-6-carboxamide mp: 140-144 ° C IR ( KBr): 1644, 1623, 1604, 1460, 1394 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.30 (3H, d, J = 7
Hz), 1.80 (2H, sextet, J = 7Hz), 2.98 (1H, dd, J = 15,7H
z), 3.17 (2H, t, J = 7Hz), 3.39 (1H, dd, J = 15,7Hz), 3.40
(3H, s), 7.10 (1H, sextet, J = 7Hz), 7.55 (1H, dd, J = 8,
1Hz), 8.02 (1H, d, J = 8Hz), 8.10 (1H, d, J = 1Hz), 9.60
(1H, br s) MASS (m / z): 303 (M+ +1), 74 (bp)
【０１９１】製造例53 ３−クロトニル−２−プロピルインドール−６−カルボ
ン酸メチルエステルから、製造例８−(1)と同様にし
て、次の化合物を製造した。 ３−（３−メトキシブタノイル）−２−プロピルインド
ール−６−カルボン酸 mp : 286−288℃ (分解) IR (KBr) : 3288, 1685, 1645, 1620 cm-1 NMR (DMSO-d6,δ) : 0.96 (3H,t,J=7Hz), 1.19 (3H,d,J
=7Hz), 1.73 (2H,sextet,J=7Hz), 2.90 (1H,dd,J=15, 7
Hz), 3.08 (2H,t,J=7Hz), 3.13(3H,s), 3.15 (1H,dd,J=
15, 7Hz), 3.91 (1H,sextet,J=7Hz), 7.26 (1H,d,J=8H
z), 7.99 (1H,s), 8.00 (1H,d,J=8Hz) MASS (m/z) : 302 (M+-1), 98 (bp)Production Example 53 The following compound was produced from 3-crotonyl-2-propylindole-6-carboxylic acid methyl ester in the same manner as in Production Example 8- (1). 3- (3-methoxybutanoyl) -2-propylindole-6-carboxylic acid mp: 286-288 ° C (decomposition) IR (KBr): 3288, 1685, 1645, 1620 cm-1 NMR (DMSO-d6 , δ): 0.96 (3H, t, J = 7Hz), 1.19 (3H, d, J
= 7Hz), 1.73 (2H, sextet, J = 7Hz), 2.90 (1H, dd, J = 15,7
Hz), 3.08 (2H, t, J = 7Hz), 3.13 (3H, s), 3.15 (1H, dd, J =
15,7Hz), 3.91 (1H, sextet, J = 7Hz), 7.26 (1H, d, J = 8H
z), 7.99 (1H, s), 8.00 (1H, d, J = 8Hz) MASS (m / z): 302 (M+ -1), 98 (bp)
【０１９２】製造例54 ３−アセチル−２−プロピルインドール−６−カルボン
酸メチルエステル（74mg）のジメチルホルムアミド（1.
4ml）溶液に、水素化ナトリウム（60％、15.4mg）を加
えた。混合物を20℃で30分間撹拌し、つぎに、臭化２−
クロロベンジル（0.045ml）を加えた。１時間撹拌後、
混合物を酢酸エチルで希釈し、水および食塩水で洗っ
た。有機層を硫酸ナトリウムで乾燥し、減圧下で溶媒を
蒸発させて、３−アセチル−１−（２−クロロベンジ
ル）−２−プロピルインドール−６−カルボン酸メチル
エステル（125mg）を固体として得た。 NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.63 (2H,m),
2.74 (3H,s), 3.05(2H,m), 3.89 (3H,s), 5.49 (2H,s),
6.22 (1H,d,J=8Hz), 7.03 (1H,t,J=8Hz), 7.20 (1H,t,
J=8Hz), 7.46 (1H,d,J=8Hz), 7.93 (1H,s), 7.97(1H,d,
J=8Hz), 8.04 (1H,d,J=8Hz)Production Example 54 3-Acetyl-2-propylindole-6-carboxylic acid methyl ester (74 mg) in dimethylformamide (1.
4 ml) solution was added sodium hydride (60%, 15.4 mg). The mixture was stirred at 20 ° C. for 30 minutes and then the bromide 2-
Chlorobenzyl (0.045 ml) was added. After stirring for 1 hour,
The mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure to give 3-acetyl-1- (2-chlorobenzyl) -2-propylindole-6-carboxylic acid methyl ester (125 mg) as a solid. . NMR (CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.63 (2H, m),
2.74 (3H, s), 3.05 (2H, m), 3.89 (3H, s), 5.49 (2H, s),
6.22 (1H, d, J = 8Hz), 7.03 (1H, t, J = 8Hz), 7.20 (1H, t,
J = 8Hz), 7.46 (1H, d, J = 8Hz), 7.93 (1H, s), 7.97 (1H, d,
J = 8Hz), 8.04 (1H, d, J = 8Hz)
【０１９３】製造例55 ３−アセチル−１−（２−クロロベンジル）−２−プロ
ピルインドール−６−カルボン酸メチルエステル（125m
g）のエタノール（６ml）溶液に、１Ｎ水酸化ナトリウ
ム水溶液（0.7ml）を加え、混合物を１時間還流下に撹
拌した。生じた混合物を減圧下で蒸発させ、残留物を１
Ｎ塩酸（0.75ml）で酸性化し、酢酸エチルで抽出した。
抽出液を食塩水で洗い、硫酸ナトリウムで乾燥し、減圧
下で蒸発させた。残留物をイソプロピルエーテルを用い
て粉末化して、３−アセチル−１−（２−クロロベンジ
ル）−２−プロピルインドール−６−カルボン酸（78m
g）を固体として得た。 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.61 (2H,m),
2.76 (3H,s), 3.08(2H,m), 5.52 (2H,s), 6.24 (1H,d,J
=8Hz), 7.04 (1H,t,J=8Hz), 7.22(1H,t,J=8Hz), 7.46
(1H,d,J=8Hz), 7.99 (1H,s), 8.03 (1H,d,J=8Hz),8.08
(1H,d,J=8Hz)Production Example 55 3-acetyl-1- (2-chlorobenzyl) -2-propylindole-6-carboxylic acid methyl ester (125 m
To a solution of g) in ethanol (6 ml) was added a 1N aqueous sodium hydroxide solution (0.7 ml) and the mixture was stirred under reflux for 1 hour. The resulting mixture was evaporated under reduced pressure and the residue was
Acidified with N hydrochloric acid (0.75 ml) and extracted with ethyl acetate.
The extract was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was triturated with isopropyl ether to give 3-acetyl-1- (2-chlorobenzyl) -2-propylindole-6-carboxylic acid (78 m
g) was obtained as a solid. NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.61 (2H, m),
2.76 (3H, s), 3.08 (2H, m), 5.52 (2H, s), 6.24 (1H, d, J
= 8Hz), 7.04 (1H, t, J = 8Hz), 7.22 (1H, t, J = 8Hz), 7.46
(1H, d, J = 8Hz), 7.99 (1H, s), 8.03 (1H, d, J = 8Hz), 8.08
(1H, d, J = 8Hz)
【０１９４】製造例56 ３−アセチル−１−（２−クロロベンジル）−２−プロ
ピルインドール−６−カルボン酸（74mg）のジメチルホ
ルムアミド（２ml）溶液に、１−ヒドロキシベンゾトリ
アゾール（38mg）、１−（３−ジメチルアミノプロピ
ル）−３−エチルカルボジイミド塩酸塩（98mg）および
３Ｎアンモニア−メタノール溶液(0.5ml)を加えた。20
℃で14時間撹拌後、生じた混合物を酢酸エチルで希釈し
た。有機層を１Ｎ塩酸、水、炭酸ナトリウム水溶液およ
び食塩水で順次洗い、硫酸ナトリウムで乾燥し、減圧下
で蒸発させた。残留物をイソプロピルエーテルを用いて
粉末化して、３−アセチル−１−（２−クロロベンジ
ル）−２−プロピルインドール−６−カルボキサミド
（67mg）を無色結晶として得た。 mp : 208−211℃ NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.61 (2H,m),
2.73 (3H,s), 3.06(2H,m), 5.49 (2H,s), 6.22 (1H,dd,
J=1, 8Hz), 7.02 (1H,dt,J=1,8Hz), 7.21 (1H,dt,J=1,
8Hz), 7.45 (1H,dd,J=1, 8Hz), 7.63 (1H,dd,J=1, 8H
z), 7.84 (1H,d,J=8Hz), 8.07 (1H,d,J=8Hz)Preparation Example 56 3-Hydroxybenzotriazole (38 mg) was added to a solution of 3-acetyl-1- (2-chlorobenzyl) -2-propylindole-6-carboxylic acid (74 mg) in dimethylformamide (2 ml). -(3-Dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (98 mg) and 3N ammonia-methanol solution (0.5 ml) were added. 20
After stirring at C for 14 hours, the resulting mixture was diluted with ethyl acetate. The organic layer was washed successively with 1N hydrochloric acid, water, aqueous sodium carbonate solution and brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was triturated with isopropyl ether to give 3-acetyl-1- (2-chlorobenzyl) -2-propylindole-6-carboxamide (67 mg) as colorless crystals. mp: 208-211 ° C NMR (CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.61 (2H, m),
2.73 (3H, s), 3.06 (2H, m), 5.49 (2H, s), 6.22 (1H, dd,
J = 1, 8Hz), 7.02 (1H, dt, J = 1,8Hz), 7.21 (1H, dt, J = 1,
8Hz), 7.45 (1H, dd, J = 1,8Hz), 7.63 (1H, dd, J = 1,8H
z), 7.84 (1H, d, J = 8Hz), 8.07 (1H, d, J = 8Hz)
【０１９５】製造例57 ３−イソブチリル−２−プロピルインドール−６−カル
ボン酸メチルエステル（440mg）と臭化２−クロロベン
ジル（346mg）とから、製造例54と同様にして、１−
（２−クロロベンジル）−３−イソブチリル−２−プロ
ピルインドール−６−カルボン酸メチルエステル（533m
g）を製造した。 NMR (CDCl3,δ) : 1.01 (3H,t,J=8Hz), 1.30 (6H,d,J=8
Hz), 1.55-1.66 (2H,m), 3.02-3.07 (2H,m), 3.58 (2H,
septet,J=8Hz), 3.90 (3H,s), 5.50(2H,s), 6.24 (1H,d
d,J=1, 8Hz), 7.05 (1H,dt,J=1, 8Hz), 7.24 (1H,dt,J=
1, 8Hz), 7.46 (1H,dd,J=1, 8Hz), 7.95 (1H,s), 7.97
(2H,s)Production Example 57 From 3-isobutyryl-2-propylindole-6-carboxylic acid methyl ester (440 mg) and 2-chlorobenzyl bromide (346 mg), 1-
(2-Chlorobenzyl) -3-isobutyryl-2-propylindole-6-carboxylic acid methyl ester (533m
g) was prepared. NMR (CDCl3 , δ): 1.01 (3H, t, J = 8Hz), 1.30 (6H, d, J = 8
Hz), 1.55-1.66 (2H, m), 3.02-3.07 (2H, m), 3.58 (2H, m
septet, J = 8Hz), 3.90 (3H, s), 5.50 (2H, s), 6.24 (1H, d
d, J = 1, 8Hz), 7.05 (1H, dt, J = 1, 8Hz), 7.24 (1H, dt, J =
1,8Hz), 7.46 (1H, dd, J = 1, 8Hz), 7.95 (1H, s), 7.97
(2H, s)
【０１９６】製造例58 １−（２−クロロベンジル）−３−イソブチリル−２−
プロピルインドール−６−カルボン酸メチルエステル
（510mg）から、製造例55と同様にして、１−（２−ク
ロロベンジル）−３−イソブチリル−２−プロピルイン
ドール−６−カルボン酸（450mg）を製造した。 NMR (DMSO-d6,δ) : 0.92 (3H,t,J=8Hz), 1.18 (6H,d,J
=8Hz), 1.38-1.52(2H,m), 3.02-3.08 (2H,m), 3.55 (2
H,septet,J=8Hz), 5.68 (2H,s),6.28 (1H,dd,J=1, 8H
z), 7.18 (1H,dt,J=1, 8Hz), 7.32 (1H,dt,J=1,8Hz),
7.52 (1H,dd,J=1, 8Hz), 7.84 (1H,dd,J=1, 8Hz), 7.97
(1H,d,J=1Hz), 8.00 (1H,d,J=8Hz)Production Example 58 1- (2-chlorobenzyl) -3-isobutyryl-2-
1- (2-Chlorobenzyl) -3-isobutyryl-2-propylindole-6-carboxylic acid (450 mg) was produced from propylindole-6-carboxylic acid methyl ester (510 mg) in the same manner as in Production Example 55. . NMR (DMSO-d6 , δ): 0.92 (3H, t, J = 8Hz), 1.18 (6H, d, J
= 8Hz), 1.38-1.52 (2H, m), 3.02-3.08 (2H, m), 3.55 (2
H, septet, J = 8Hz), 5.68 (2H, s), 6.28 (1H, dd, J = 1,8H
z), 7.18 (1H, dt, J = 1,8Hz), 7.32 (1H, dt, J = 1,8Hz),
7.52 (1H, dd, J = 1,8Hz), 7.84 (1H, dd, J = 1,8Hz), 7.97
(1H, d, J = 1Hz), 8.00 (1H, d, J = 8Hz)
【０１９７】製造例59 １−（２−クロロベンジル）−３−イソブチリル−２−
プロピルインドール−６−カルボン酸（150mg）のジメ
チルホルムアミド（３ml）溶液に、１−ヒドロキシベン
ゾトリアゾール（102mg）、１−（３−ジメチルアミノ
プロピル）−３−エチルカルボジイミド塩酸塩（109m
g）を加えた。20℃で一夜撹拌後、生じた混合物を28％
アンモニア水（５ml）中に注いだ。混合物を酢酸エチル
と水とに分配し、有機層を１Ｎ塩酸および食塩水で洗
い、硫酸ナトリムで乾燥し、減圧下で蒸発させた。結晶
性残留物を酢酸エチル−ヘキサン混合物から再結晶し
て、１−（２−クロロベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボキサミド（123m
g）を無色結晶として得た。 mp : 185−186℃ NMR (CDCl3,δ) : 1.01 (3H,t,J=8Hz), 1.30 (6H,d,J=8
Hz), 1.55-1.66 (2H,m), 3.00-3.06 (2H,m), 3.56 (2H,
septet,J=8Hz), 5.49 (2H,s), 6.24(1H,dd,J=1, 8Hz),
7.04 (1H,dt,J=1, 8Hz), 7.23 (1H,dt,J=1, 8Hz),7.46
(1H,dd,J=1, 8Hz), 7.63 (1H,dd,J=1, 8Hz), 7.85 (1H,
d,J=1Hz),7.97 (1H,d,J=8Hz)Production Example 59 1- (2-chlorobenzyl) -3-isobutyryl-2-
To a solution of propylindole-6-carboxylic acid (150 mg) in dimethylformamide (3 ml) was added 1-hydroxybenzotriazole (102 mg) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (109 m2).
g) was added. After stirring at 20 ° C. overnight, the resulting mixture is reduced to 28%
Poured into aqueous ammonia (5 ml). The mixture was partitioned between ethyl acetate and water, the organic layer was washed with 1N hydrochloric acid and brine, dried over sodium sulfate and evaporated under reduced pressure. The crystalline residue was recrystallized from an ethyl acetate-hexane mixture to give 1- (2-chlorobenzyl) -3-isobutyryl-
2-propylindole-6-carboxamide (123 m
g) was obtained as colorless crystals. mp: 185-186 ° C NMR (CDCl3 , δ): 1.01 (3H, t, J = 8Hz), 1.30 (6H, d, J = 8
Hz), 1.55-1.66 (2H, m), 3.00-3.06 (2H, m), 3.56 (2H, m
septet, J = 8Hz), 5.49 (2H, s), 6.24 (1H, dd, J = 1,8Hz),
7.04 (1H, dt, J = 1,8Hz), 7.23 (1H, dt, J = 1,8Hz), 7.46
(1H, dd, J = 1,8Hz), 7.63 (1H, dd, J = 1,8Hz), 7.85 (1H,
d, J = 1Hz), 7.97 (1H, d, J = 8Hz)
【０１９８】製造例60 ３−プロピオニル−２−プロピルインドール−６−カル
ボン酸メチルエステル（260mg）と臭化２−クロロベン
ジル（215mg）とから、製造例54と同様にして、１−
（２−クロロベンジル）−３−プロピオニル−２−プロ
ピルインドール−６−カルボン酸メチルエステル（436m
g）を製造した。 NMR (CDCl3,δ) : 1.02 (3H,t,J=8Hz), 1.30 (3H,t,J=8
Hz), 1.55-1.68 (2H,m), 3.00-3.16 (4H,m), 3.90 (3H,
s), 5.49 (2H,s), 6.22 (1H,dd,J=1,8Hz), 7.05 (1H,d
t,J=1, 8Hz), 7.23 (1H,dt,J=1, 8Hz), 7.46 (1H,dd,J=
1, 8Hz), 7.93 (1H,d,J=8Hz), 7.96 (1H,dd,J=1, 8Hz),
8.03 (1H,d,J=8Hz)Production Example 60 From 3-propionyl-2-propylindole-6-carboxylic acid methyl ester (260 mg) and 2-chlorobenzyl bromide (215 mg), 1-
(2-Chlorobenzyl) -3-propionyl-2-propylindole-6-carboxylic acid methyl ester (436m
g) was prepared. NMR (CDCl3 , δ): 1.02 (3H, t, J = 8Hz), 1.30 (3H, t, J = 8
Hz), 1.55-1.68 (2H, m), 3.00-3.16 (4H, m), 3.90 (3H,
s), 5.49 (2H, s), 6.22 (1H, dd, J = 1,8Hz), 7.05 (1H, d
t, J = 1, 8Hz), 7.23 (1H, dt, J = 1, 8Hz), 7.46 (1H, dd, J =
1, 8Hz), 7.93 (1H, d, J = 8Hz), 7.96 (1H, dd, J = 1,8Hz),
8.03 (1H, d, J = 8Hz)
【０１９９】製造例61 １−（２−クロロベンジル）−３−プロピオニル−２−
プロピルインドール−６−カルボン酸メチルエステル
（425mg）から、製造例55と同様にして、１−（２−ク
ロロベンジル）−３−プロピオニル−２−プロピルイン
ドール−６−カルボン酸（308mg）を製造した。 NMR (DMSO-d6,δ) : 0.94 (3H,t,J=8Hz), 1.14 (3H,t,J
=8Hz), 1.49 (2H,sextet,J=8Hz), 3.00-3.10 (4H,m),
5.67 (2H,s), 6.27 (1H,dd,J=1,8Hz), 7.18 (1H,dt,J=
1, 8Hz), 7.32 (1H,dt,J=1, 8Hz), 7.56 (1H,dd,J=1, 8
Hz), 7.83 (1H,dd,J=1, 8Hz), 7.96 (1H,d,J=1Hz), 8.0
9 (1H,d,J=8Hz)Production Example 61 1- (2-chlorobenzyl) -3-propionyl-2-
1- (2-Chlorobenzyl) -3-propionyl-2-propylindole-6-carboxylic acid (308 mg) was produced from propylindole-6-carboxylic acid methyl ester (425 mg) in the same manner as in Production Example 55. . NMR (DMSO-d6 , δ): 0.94 (3H, t, J = 8Hz), 1.14 (3H, t, J
= 8Hz), 1.49 (2H, sextet, J = 8Hz), 3.00-3.10 (4H, m),
5.67 (2H, s), 6.27 (1H, dd, J = 1,8Hz), 7.18 (1H, dt, J =
1, 8Hz), 7.32 (1H, dt, J = 1, 8Hz), 7.56 (1H, dd, J = 1, 8
Hz), 7.83 (1H, dd, J = 1,8Hz), 7.96 (1H, d, J = 1Hz), 8.0
9 (1H, d, J = 8Hz)
【０２００】製造例62 １−（２−クロロベンジル）−３−プロピオニル−２−
プロピルインドール−６−カルボン酸（100mg）から、
製造例59と同様にして、１−（２−クロロベンジル）−
３−プロピオニル−２−プロピルインドール−６−カル
ボキサミド（81mg）を製造した。 mp : 151−152℃ NMR (CDCl3,δ) : 1.02 (3H,t,J=8Hz), 1.30 (3H,t,J=8
Hz), 1.62 (2H,sextet,J=8Hz), 3.04-3.14 (4H,m), 5.5
0 (2H,s), 6.22 (1H,dd,J=1,8Hz), 7.03 (1H,dt,J=1, 8
Hz), 7.22 (1H,dt,J=1, 8Hz), 7.45 (1H,dd,J=1, 8Hz),
7.64 (1H,dd,J=1, 8Hz), 7.84 (1H,d,J=1Hz), 8.06 (1
H,d,J=8Hz)Production Example 62 1- (2-chlorobenzyl) -3-propionyl-2-
From propylindole-6-carboxylic acid (100 mg)
In the same manner as in Production Example 59, 1- (2-chlorobenzyl)-
3-Propionyl-2-propylindole-6-carboxamide (81 mg) was prepared. mp: 151-152 ° C NMR (CDCl3 , δ): 1.02 (3H, t, J = 8Hz), 1.30 (3H, t, J = 8
Hz), 1.62 (2H, sextet, J = 8Hz), 3.04-3.14 (4H, m), 5.5
0 (2H, s), 6.22 (1H, dd, J = 1,8Hz), 7.03 (1H, dt, J = 1,8
Hz), 7.22 (1H, dt, J = 1,8Hz), 7.45 (1H, dd, J = 1,8Hz),
7.64 (1H, dd, J = 1,8Hz), 7.84 (1H, d, J = 1Hz), 8.06 (1
(H, d, J = 8Hz)
【０２０１】製造例63 ２−イソブチル−３−イソブチリルインドール−６−カ
ルボン酸メチルエステル（210mg）と臭化２−クロロベ
ンジル（157mg）とから、製造例54と同様にして、１−
（２−クロロベンジル）−２−イソブチル−３−イソブ
チリルインドール−６−カルボン酸メチルエステル（25
8mg）を製造した。 NMR (CDCl3,δ) : 0.97 (6H,d,J=7Hz), 1.31 (6H,d,J=7
Hz), 1.96-2.10(1H,m), 3.04 (2H,d,J=7Hz), 3.60 (1H,
septet,J=7Hz), 3.90 (3H,s),5.53 (2H,s), 6.18 (1H,
d,J=8Hz), 7.04 (1H,t,J=8Hz), 7.23 (1H,t,J=8Hz), 7.
46 (1H,t,J=8Hz), 7.94 (1H,s), 7.96 (2H,s)Production Example 63 2-isobutyl-3-isobutyrylindole-6-carboxylic acid methyl ester (210 mg) and 2-chlorobenzyl bromide (157 mg) were treated in the same manner as in Production Example 54 to give 1-
(2-chlorobenzyl) -2-isobutyl-3-isobutyrylindole-6-carboxylic acid methyl ester (25
8 mg). NMR (CDCl3 , δ): 0.97 (6H, d, J = 7Hz), 1.31 (6H, d, J = 7
Hz), 1.96-2.10 (1H, m), 3.04 (2H, d, J = 7Hz), 3.60 (1H,
septet, J = 7Hz), 3.90 (3H, s), 5.53 (2H, s), 6.18 (1H,
d, J = 8Hz), 7.04 (1H, t, J = 8Hz), 7.23 (1H, t, J = 8Hz), 7.
46 (1H, t, J = 8Hz), 7.94 (1H, s), 7.96 (2H, s)
【０２０２】製造例64 １−（２−クロロベンジル）−２−イソブチル−３−イ
ソブチリルインドール−６−カルボン酸メチルエステル
（213mg）から、製造例55と同様にして、１−（２−ク
ロロベンジル）−２−イソブチル−３−イソブチリルイ
ンドール−６−カルボン酸（184mg）を製造した。 NMR (DMSO-d6,δ) : 0.88 (6H,d,J=8Hz), 1.17 (6H,d,J
=7Hz), 1.82-1.95(1H,m), 3.07 (2H,d,J=8Hz), 3.57 (1
H,septet,J=7Hz), 5.68 (2H,s),6.25 (1H,d,J=8Hz), 7.
18 (1H,t,J=8Hz), 7.33 (1H,t,J=8Hz), 7.57(1H,d,J=8H
z), 7.85 (1H,d,J=8Hz), 7.95 (1H,s), 8.00 (1H,d,J=8
Hz)Production Example 64 1- (2-Chlorobenzyl) -2-isobutyl-3-isobutyrylindole-6-carboxylic acid methyl ester (213 mg) was prepared in the same manner as in Production Example 55 by using 1- (2-chlorobenzyl) methyl ester (213 mg). (Chlorobenzyl) -2-isobutyl-3-isobutyrylindole-6-carboxylic acid (184 mg) was prepared. NMR (DMSO-d6 , δ): 0.88 (6H, d, J = 8Hz), 1.17 (6H, d, J
= 7Hz), 1.82-1.95 (1H, m), 3.07 (2H, d, J = 8Hz), 3.57 (1
(H, septet, J = 7Hz), 5.68 (2H, s), 6.25 (1H, d, J = 8Hz), 7.
18 (1H, t, J = 8Hz), 7.33 (1H, t, J = 8Hz), 7.57 (1H, d, J = 8H)
z), 7.85 (1H, d, J = 8Hz), 7.95 (1H, s), 8.00 (1H, d, J = 8
Hz)
【０２０３】製造例65 １−（２−クロロベンジル）−２−イソブチル−３−イ
ソブチリルインドール−６−カルボン酸（160mg）か
ら、製造例59と同様にして、１−（２−クロロベンジ
ル）−２−イソブチル−３−イソブチリルインドール−
６−カルボキサミド（143mg）を製造した。 NMR (DMSO-d6,δ) : 0.86 (6H,d,J=8Hz), 1.17 (6H,d,J
=7Hz), 1.80-1.94(1H,m), 3.02 (2H,d,J=8Hz), 3.57 (1
H,septet,J=7Hz), 5.62 (2H,s),6.16 (1H,d,J=8Hz), 7.
18 (1H,t,J=8Hz), 7.30-7.35 (2H,m), 7.57 (1H,d,J=8H
z), 7.82 (1H,d,J=8Hz), 7.94 (1H,s), 7.96 (1H,d,J=8
Hz), 8.00(1H,s)Production Example 65 1- (2-Chlorobenzyl) -2-isobutyl-3-isobutyrylindole-6-carboxylic acid (160 mg) was prepared in the same manner as in Production Example 59 by using 1- (2-chlorobenzyl). ) -2-Isobutyl-3-isobutyrylindole-
6-carboxamide (143 mg) was prepared. NMR (DMSO-d6 , δ): 0.86 (6H, d, J = 8Hz), 1.17 (6H, d, J
= 7Hz), 1.80-1.94 (1H, m), 3.02 (2H, d, J = 8Hz), 3.57 (1
(H, septet, J = 7Hz), 5.62 (2H, s), 6.16 (1H, d, J = 8Hz), 7.
18 (1H, t, J = 8Hz), 7.30-7.35 (2H, m), 7.57 (1H, d, J = 8H
z), 7.82 (1H, d, J = 8Hz), 7.94 (1H, s), 7.96 (1H, d, J = 8
Hz), 8.00 (1H, s)
【０２０４】製造例66 ２−エチル−３−プロピオニルインドール−６−カルボ
ン酸メチルエステル（215mg）と臭化２−クロロベンジ
ル（0.24ml）とから、製造例54と同様にして、１−（２
−クロロベンジル）−２−エチル−３−プロピオニルイ
ンドール−６−カルボン酸メチルエステル（278mg）を
製造した。 NMR (CDCl3,δ) : 1.22 (3H,t,J=7Hz), 1.30 (3H,t,J=7
Hz), 3.05-3.20 (4H,m), 3.90 (3H,s), 5.50 (2H,s),
6.22 (1H,d,J=8Hz), 7.02 (1H,t,J=8Hz), 7.20 (1H,t,J
=8Hz), 7.46 (1H,d,J=8Hz), 7.92 (1H,s), 7.95(1H,d,J
=8Hz), 8.04 (1H,d,J=8Hz)Production Example 66 2- (3-propionylindole-6-carboxylic acid methyl ester (215 mg) and 2-chlorobenzyl bromide (0.24 ml) were prepared in the same manner as in Production Example 54 by using 1- (2
-Chlorobenzyl) -2-ethyl-3-propionylindole-6-carboxylic acid methyl ester (278 mg) was prepared. NMR (CDCl3 , δ): 1.22 (3H, t, J = 7Hz), 1.30 (3H, t, J = 7
Hz), 3.05-3.20 (4H, m), 3.90 (3H, s), 5.50 (2H, s),
6.22 (1H, d, J = 8Hz), 7.02 (1H, t, J = 8Hz), 7.20 (1H, t, J
= 8Hz), 7.46 (1H, d, J = 8Hz), 7.92 (1H, s), 7.95 (1H, d, J
= 8Hz), 8.04 (1H, d, J = 8Hz)
【０２０５】製造例67 １−（２−クロロベンジル）−２−エチル−３−プロピ
オニルインドール−６−カルボン酸メチルエステル（45
3mg）から、製造例55と同様にして、１−（２−クロロ
ベンジル）−２−エチル−３−プロピオニルインドール
−６−カルボン酸（417mg）を製造した。 NMR (DMSO-d6,δ) : 1.09 (3H,t,J=7Hz), 1.17 (3H,t,J
=7Hz), 3.08 (2H,t,J=7Hz), 3.11 (2H,t,J=7Hz), 5.68
(2H,s), 6.24 (1H,d,J=8Hz), 7.18(1H,t,J=8Hz), 7.31
(1H,t,J=8Hz), 7.57 (1H,d,J=8Hz), 7.83 (1H,d,J=8H
z), 7.95 (1H,s), 8.13 (1H,d,J=8Hz)Production Example 67 1- (2-Chlorobenzyl) -2-ethyl-3-propionylindole-6-carboxylic acid methyl ester (45
From 3 mg), 1- (2-chlorobenzyl) -2-ethyl-3-propionylindole-6-carboxylic acid (417 mg) was produced in the same manner as in Production Example 55. NMR (DMSO-d6 , δ): 1.09 (3H, t, J = 7Hz), 1.17 (3H, t, J
= 7Hz), 3.08 (2H, t, J = 7Hz), 3.11 (2H, t, J = 7Hz), 5.68
(2H, s), 6.24 (1H, d, J = 8Hz), 7.18 (1H, t, J = 8Hz), 7.31
(1H, t, J = 8Hz), 7.57 (1H, d, J = 8Hz), 7.83 (1H, d, J = 8H
z), 7.95 (1H, s), 8.13 (1H, d, J = 8Hz)
【０２０６】製造例68 １−（２−クロロベンジル）−２−エチル−３−プロピ
オニルインドール−６−カルボン酸（252mg）から、製
造例56と同様にして、１−（２−クロロベンジル）−２
−エチル−３−プロピオニルインドール−６−カルボキ
サミド(242mg)を製造した。 NMR (CDCl3,δ) : 1.23 (3H,t,J=7Hz), 1.29 (3H,t,J=7
Hz), 3.08-3.18 (4H,m), 5.49 (2H,s), 6.19 (1H,d,J=8
Hz), 7.02 (1H,t,J=8Hz), 7.21 (1H,t,J=8Hz), 7.46 (1
H,d,J=8Hz), 7.62 (1H,d,J=8Hz), 7.83 (1H,s), 8.09(1
H,d,J=8Hz)Production Example 68 1- (2-Chlorobenzyl) -2-ethyl-3-propionylindole-6-carboxylic acid (252 mg) was prepared in the same manner as in Production Example 56 by using 1- (2-chlorobenzyl)- 2
-Ethyl-3-propionylindole-6-carboxamide (242 mg) was prepared. NMR (CDCl3 , δ): 1.23 (3H, t, J = 7Hz), 1.29 (3H, t, J = 7
Hz), 3.08-3.18 (4H, m), 5.49 (2H, s), 6.19 (1H, d, J = 8
Hz), 7.02 (1H, t, J = 8Hz), 7.21 (1H, t, J = 8Hz), 7.46 (1
H, d, J = 8Hz), 7.62 (1H, d, J = 8Hz), 7.83 (1H, s), 8.09 (1
(H, d, J = 8Hz)
【０２０７】製造例69 ２−アセチル−３−イソブチルインドール−６−カルボ
ン酸メチルエステル（58mg）と臭化２−クロロベンジル
（0.04ml）とから、製造例54と同様にして、２−アセチ
ル−１−（２−クロロベンジル）−３−イソブチルイン
ドール−６−カルボン酸メチルエステル（71.4mg）を製
造した。 NMR (CDCl3,δ) : 1.02 (6H,d,J=7Hz), 2.02 (1H,m),
2.59 (3H,s), 3.01(2H,d,J=7Hz), 3.90 (3H,s), 5.84
(2H,s), 6.19 (1H,d,J=8Hz), 6.99(1H,t,J=8Hz), 7.15
(1H,t,J=8Hz), 7.40 (1H,d,J=8Hz), 7.75 (1H,d,J=8H
z), 7.83 (1H,d,J=8Hz), 7.98 (1H,s)Production Example 69 2-acetyl-3-isobutylindole-6-carboxylic acid methyl ester (58 mg) and 2-chlorobenzyl bromide (0.04 ml) were prepared in the same manner as in Production Example 54, using 2-acetyl- 1- (2-Chlorobenzyl) -3-isobutylindole-6-carboxylic acid methyl ester (71.4 mg) was produced. NMR (CDCl3 , δ): 1.02 (6H, d, J = 7Hz), 2.02 (1H, m),
2.59 (3H, s), 3.01 (2H, d, J = 7Hz), 3.90 (3H, s), 5.84
(2H, s), 6.19 (1H, d, J = 8Hz), 6.99 (1H, t, J = 8Hz), 7.15
(1H, t, J = 8Hz), 7.40 (1H, d, J = 8Hz), 7.75 (1H, d, J = 8H
z), 7.83 (1H, d, J = 8Hz), 7.98 (1H, s)
【０２０８】製造例70 ２−アセチル−１−（２−クロロベンジル）−３−イソ
ブチルインドール−６−カルボン酸メチルエステル（67
mg）から、製造例55と同様にして、２−アセチル−１−
（２−クロロベンジル）−３−イソブチルインドール−
６−カルボン酸（45.3mg）を製造した。 NMR (CDCl3,δ) : 1.02 (6H,d,J=7Hz), 2.03 (1H,m),
2.62 (3H,s), 3.03(2H,d,J=7Hz), 5.76 (2H,s), 6.19
(1H,d,J=8Hz), 7.00 (1H,t,J=8Hz),7.14 (1H,t,J=8Hz),
7.41 (1H,d,J=8Hz), 7.77 (1H,d,J=8Hz), 7.86 (1H,d,
J=8Hz), 8.02 (1H,s)Production Example 70 2-acetyl-1- (2-chlorobenzyl) -3-isobutylindole-6-carboxylic acid methyl ester (67
mg), in the same manner as in Production Example 55, 2-acetyl-1-
(2-chlorobenzyl) -3-isobutylindole-
6-Carboxylic acid (45.3 mg) was prepared. NMR (CDCl3 , δ): 1.02 (6H, d, J = 7Hz), 2.03 (1H, m),
2.62 (3H, s), 3.03 (2H, d, J = 7Hz), 5.76 (2H, s), 6.19
(1H, d, J = 8Hz), 7.00 (1H, t, J = 8Hz), 7.14 (1H, t, J = 8Hz),
7.41 (1H, d, J = 8Hz), 7.77 (1H, d, J = 8Hz), 7.86 (1H, d,
J = 8Hz), 8.02 (1H, s)
【０２０９】製造例71 ２−アセチル−１−（２−クロロベンジル）−３−イソ
ブチルインドール−６−カルボン酸（41.7mg）から、製
造例56と同様にして、２−アセチル−１−（２−クロロ
ベンジル）−３−イソブチルインドール−６−カルボキ
サミド（33.4mg）を製造した。 NMR (CDCl3,δ) : 1.01 (6H,d,J=7Hz), 2.02 (1H,m),
2.62 (3H,s), 3.03(2H,d,J=7Hz), 5.54 (2H,s), 6.22
(1H,d,J=8Hz), 6.99 (1H,t,J=8Hz),7.16 (1H,t,J=8Hz),
7.41 (1H,d,J=8Hz), 7.54 (1H,d,J=8Hz), 7.78(1H,d,J
=8Hz), 7.79 (1H,s)Production Example 71 2-Acetyl-1- (2-chlorobenzyl) -3-isobutylindole-6-carboxylic acid (41.7 mg) was prepared in the same manner as in Production Example 56, using 2-acetyl-1- (2 -Chlorobenzyl) -3-isobutylindole-6-carboxamide (33.4 mg) was prepared. NMR (CDCl3 , δ): 1.01 (6H, d, J = 7Hz), 2.02 (1H, m),
2.62 (3H, s), 3.03 (2H, d, J = 7Hz), 5.54 (2H, s), 6.22
(1H, d, J = 8Hz), 6.99 (1H, t, J = 8Hz), 7.16 (1H, t, J = 8Hz),
7.41 (1H, d, J = 8Hz), 7.54 (1H, d, J = 8Hz), 7.78 (1H, d, J
= 8Hz), 7.79 (1H, s)
【０２１０】製造例72 ３−エチル−２−プロピオニルインドール−６−カルボ
ン酸メチル（88mg）と臭化２−クロロベンジル（0.051m
l）とから、製造例54と同様にして、１−（２−クロロ
ベンジル）−３−エチル−２−プロピオニルインドール
−６−カルボン酸メチルエステル（66mg）を製造した。 NMR (CDCl3,δ) : 1.16 (3H,t,J=7Hz), 1.38 (3H,t,J=7
Hz), 2.95 (2H,q,J=7Hz), 3.14 (2H,q,J=7Hz), 3.90 (3
H,s), 5.72 (2H,s), 6.23 (1H,d,J=8Hz), 6.98 (1H,t,J
=8Hz), 7.14 (1H,t,J=8Hz), 7.39 (1H,d,J=8Hz),7.77
(1H,d,J=8Hz), 7.85 (1H,d,J=8Hz), 7.97 (1H,s)Production Example 72 Methyl 3-ethyl-2-propionylindole-6-carboxylate (88 mg) and 2-chlorobenzyl bromide (0.051 m
l) to give 1- (2-chlorobenzyl) -3-ethyl-2-propionylindole-6-carboxylic acid methyl ester (66 mg) in the same manner as in Production Example 54. NMR (CDCl3 , δ): 1.16 (3H, t, J = 7Hz), 1.38 (3H, t, J = 7
Hz), 2.95 (2H, q, J = 7Hz), 3.14 (2H, q, J = 7Hz), 3.90 (3
H, s), 5.72 (2H, s), 6.23 (1H, d, J = 8Hz), 6.98 (1H, t, J
= 8Hz), 7.14 (1H, t, J = 8Hz), 7.39 (1H, d, J = 8Hz), 7.77
(1H, d, J = 8Hz), 7.85 (1H, d, J = 8Hz), 7.97 (1H, s)
【０２１１】製造例73 １−（２−クロロベンジル）−３−エチル−２−プロピ
オニルインドール−６−カルボン酸メチルエステル（5
9.4mg）から、製造例55と同様にして、１−（２−クロ
ロベンジル）−３−エチル−２−プロピオニルインドー
ル−６−カルボン酸（48.7mg）を製造した。 NMR (CDCl3,δ) : 1.16 (3H,t,J=7Hz), 1.37 (3H,t,J=7
Hz), 2.94 (2H,q,J=7Hz), 3.15 (2H,q,J=7Hz), 5.72 (2
H,s), 6.25 (1H,d,J=8Hz), 6.99(1H,t,J=8Hz), 7.15 (1
H,t,J=8Hz), 7.40 (1H,d,J=8Hz), 7.78 (1H,d,J=8Hz),
7.87 (1H,d,J=8Hz), 8.01 (1H,s)Production Example 73 1- (2-Chlorobenzyl) -3-ethyl-2-propionylindole-6-carboxylic acid methyl ester (5
In the same manner as in Production Example 55, 1- (2-chlorobenzyl) -3-ethyl-2-propionylindole-6-carboxylic acid (48.7 mg) was produced from 9.4 mg). NMR (CDCl3 , δ): 1.16 (3H, t, J = 7Hz), 1.37 (3H, t, J = 7
Hz), 2.94 (2H, q, J = 7Hz), 3.15 (2H, q, J = 7Hz), 5.72 (2H
H, s), 6.25 (1H, d, J = 8Hz), 6.99 (1H, t, J = 8Hz), 7.15 (1
H, t, J = 8Hz), 7.40 (1H, d, J = 8Hz), 7.78 (1H, d, J = 8Hz),
7.87 (1H, d, J = 8Hz), 8.01 (1H, s)
【０２１２】製造例74 １−（２−クロロベンジル）−３−エチル−２−プロピ
オニルインドール−６−カルボン酸（46mg）から、製造
例56と同様にして、１−（２−クロロベンジル）−３−
エチル−２−プロピオニルインドール−６−カルボキサ
ミド（40.4mg）を製造した。 NMR (CDCl3,δ) : 1.16 (3H,t,J=7Hz), 1.38 (3H,t,J=7
Hz), 2.96 (2H,q,J=7Hz), 3.14 (2H,q,J=7Hz), 5.72 (2
H,s), 6.25 (1H,d,J=8Hz), 7.00(1H,t,J=8Hz), 7.14 (1
H,t,J=8Hz), 7.39 (1H,d,J=8Hz), 7.56 (1H,d,J=8Hz),
7.79 (1H,s), 7.80 (1H,d,J=8Hz)Production Example 74 1- (2-Chlorobenzyl) -3-ethyl-2-propionylindole-6-carboxylic acid (46 mg) was prepared in the same manner as in Production Example 56 by using 1- (2-chlorobenzyl)- 3-
Ethyl-2-propionylindole-6-carboxamide (40.4 mg) was prepared. NMR (CDCl3 , δ): 1.16 (3H, t, J = 7Hz), 1.38 (3H, t, J = 7
Hz), 2.96 (2H, q, J = 7Hz), 3.14 (2H, q, J = 7Hz), 5.72 (2H
H, s), 6.25 (1H, d, J = 8Hz), 7.00 (1H, t, J = 8Hz), 7.14 (1
H, t, J = 8Hz), 7.39 (1H, d, J = 8Hz), 7.56 (1H, d, J = 8Hz),
7.79 (1H, s), 7.80 (1H, d, J = 8Hz)
【０２１３】製造例75 製造例55または製造例87−(19)で得た化合物（Ｉ−２）
と適当なアミン（IV）とを、製造例56と同様に反応させ
て、次の(1)〜(6)に記載の化合物を製造した。 (1) ３−アセチル−１−（２−クロロベンジル）−Ｎ,
Ｎ−ジメチル−２−プロピルインドール−６−カルボキ
サミド mp : 150−153℃ NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.63 (2H,m),
2.72 (3H,s), 2.98(6H,br s), 3.09 (2H,m), 5.44 (2H,
s), 6.26 (1H,dd,J=1, 8Hz), 7.03(1H,dt,J=1, 8Hz),
7.20 (1H,dt,J=1, 8Hz), 7.29 (1H,s), 7.35 (1H,d,J=8
Hz), 7.43 (1H,dd,J=1, 8Hz), 8.03 (1H,d,J=8Hz) (2) ３−アセチル−１−（２−クロロベンジル）−Ｎ−
シクロプロピルメチル−２−プロピルインドール−６−
カルボキサミド mp : 158−162℃ NMR (CDCl3,δ) : 0.28 (2H,m), 0.55 (2H,m), 1.03 (3
H,t,J=7Hz), 1.05(1H,m), 1.60 (2H,m), 2.72 (3H,s),
3.04 (2H,m), 3.31 (2H,m), 5.49(2H,s), 6.22 (1H,d,J
=8Hz), 6.28 (1H,m), 7.03 (1H,t,J=8Hz), 7.22(1H,t,J
=8Hz), 7.45 (1H,d,J=8Hz), 7.61 (1H,dd,J=1, 8Hz),
7.82 (1H,d,J=1Hz), 8.05 (1H,d,J=8Hz)Production Example 75 Compound (I-2) obtained in Production Example 55 or 87- (19)
And the appropriate amine (IV) were reacted in the same manner as in Production Example 56 to produce the following compounds described in (1) to (6). (1) 3-acetyl-1- (2-chlorobenzyl) -N,
N-dimethyl-2-propylindole-6-carboxamide mp: 150-153 ° C NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.63 (2H, m),
2.72 (3H, s), 2.98 (6H, br s), 3.09 (2H, m), 5.44 (2H,
s), 6.26 (1H, dd, J = 1,8Hz), 7.03 (1H, dt, J = 1,8Hz),
7.20 (1H, dt, J = 1,8Hz), 7.29 (1H, s), 7.35 (1H, d, J = 8
Hz), 7.43 (1H, dd, J = 1,8Hz), 8.03 (1H, d, J = 8Hz) (2) 3-acetyl-1- (2-chlorobenzyl) -N-
Cyclopropylmethyl-2-propylindole-6
Carboxamide mp: 158-162 ° C NMR (CDCl3 , δ): 0.28 (2H, m), 0.55 (2H, m), 1.03 (3
(H, t, J = 7Hz), 1.05 (1H, m), 1.60 (2H, m), 2.72 (3H, s),
3.04 (2H, m), 3.31 (2H, m), 5.49 (2H, s), 6.22 (1H, d, J
= 8Hz), 6.28 (1H, m), 7.03 (1H, t, J = 8Hz), 7.22 (1H, t, J
= 8Hz), 7.45 (1H, d, J = 8Hz), 7.61 (1H, dd, J = 1,8Hz),
7.82 (1H, d, J = 1Hz), 8.05 (1H, d, J = 8Hz)
【０２１４】(3) ３−アセチル−１−（２−クロロベン
ジル）−Ｎ−（２−ピリジルメチル）−２−プロピルイ
ンドール−６−カルボキサミド mp : 172−175℃ NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.63 (2H,m),
2.73 (3H,s), 3.07(2H,m), 4.75 (2H,d,J=5Hz), 5.51
(2H,s), 6.22 (1H,d,J=8Hz), 7.02(1H,t,J=8Hz), 7.15-
7.27 (2H,m), 7.33 (1H,d,J=8Hz), 7.44 (1H,d,J=8Hz),
7.58-7.76 (3H,s), 7.88 (1H,s), 8.07 (1H,d,J=8Hz),
8.56(1H,m) (4) ３−アセチル−１−（２−クロロベンジル）−６−
（モルホリノカルボニル）−２−プロピルインドール NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.63 (2H,m),
2.73 (3H,s), 3.09(2H,m), 3.63 (8H,br s), 5.44 (2H,
s), 6.23 (1H,d,J=8Hz), 7.06 (1H,t,J=8Hz), 7.2-7.4
(3H,m), 7.46 (1H,d,J=8Hz), 8.06 (1H,d,J=8Hz)(3) 3-acetyl-1- (2-chlorobenzyl) -N- (2-pyridylmethyl) -2-propylindole-6-carboxamide mp: 172-175 ° C. NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.63 (2H, m),
2.73 (3H, s), 3.07 (2H, m), 4.75 (2H, d, J = 5Hz), 5.51
(2H, s), 6.22 (1H, d, J = 8Hz), 7.02 (1H, t, J = 8Hz), 7.15-
7.27 (2H, m), 7.33 (1H, d, J = 8Hz), 7.44 (1H, d, J = 8Hz),
7.58-7.76 (3H, s), 7.88 (1H, s), 8.07 (1H, d, J = 8Hz),
8.56 (1H, m) (4) 3-acetyl-1- (2-chlorobenzyl) -6
(Morpholinocarbonyl) -2-propyl indoleNMR (CDCl 3, δ): 1.03 (3H, t, J = 7Hz), 1.63 (2H, m),
2.73 (3H, s), 3.09 (2H, m), 3.63 (8H, br s), 5.44 (2H,
s), 6.23 (1H, d, J = 8Hz), 7.06 (1H, t, J = 8Hz), 7.2-7.4
(3H, m), 7.46 (1H, d, J = 8Hz), 8.06 (1H, d, J = 8Hz)
【０２１５】(5) ３−アセチル−１−（２−クロロベン
ジル）−Ｎ−フェニルスルホニル−２−プロピルインド
ール−６−カルボキサミド mp : 206−208℃ NMR (CDCl3,δ) : 0.99 (3H,t,J=7Hz), 1.54 (2H,m),
2.72 (3H,s), 3.02(2H,m), 5.43 (2H,s), 6.13 (1H,d,J
=8Hz), 7.00 (1H,t,J=8Hz), 7.21(1H,t,J=8Hz), 7.43
(1H,d,J=8Hz), 7.5-7.7 (4H,m), 7.77 (1H,s),8.08 (1
H,d,J=8Hz), 8.13-8.18 (2H,m), 8.81 (1H,br s) (6) １−（２−クロロベンジル）−３−ホルミル−Ｎ−
フェニルスルホニル−２−プロピルインドール−６−カ
ルボキサミド mp : 242−245℃ NMR (CDCl3,δ) : 0.87 (3H,t,J=7Hz), 1.49 (2H,m),
3.07 (2H,t,J=7Hz),5.66 (2H,s), 6.32 (1H,d,J=8Hz),
7.18 (1H,t,J=8Hz), 7.33 (1H,t,J=8Hz), 7.55-7.75 (4
H,m), 7.88 (1H,m), 7.96 (1H,s), 7.98 (1H,d,J=8Hz),
8.09 (1H,s), 8.23 (1H,d,J=8Hz)(5) 3-acetyl-1- (2-chlorobenzyl) -N-phenylsulfonyl-2-propylindole-6-carboxamide mp: 206-208 ° C. NMR (CDCl3 , δ): 0.99 (3H, t, J = 7Hz), 1.54 (2H, m),
2.72 (3H, s), 3.02 (2H, m), 5.43 (2H, s), 6.13 (1H, d, J
= 8Hz), 7.00 (1H, t, J = 8Hz), 7.21 (1H, t, J = 8Hz), 7.43
(1H, d, J = 8Hz), 7.5-7.7 (4H, m), 7.77 (1H, s), 8.08 (1
H, d, J = 8Hz), 8.13-8.18 (2H, m), 8.81 (1H, brs) (6) 1- (2-chlorobenzyl) -3-formyl-N-
Phenylsulfonyl-2-propylindole-6-carboxamide mp: 242-245 ° C NMR (CDCl3 , δ): 0.87 (3H, t, J = 7Hz), 1.49 (2H, m),
3.07 (2H, t, J = 7Hz), 5.66 (2H, s), 6.32 (1H, d, J = 8Hz),
7.18 (1H, t, J = 8Hz), 7.33 (1H, t, J = 8Hz), 7.55-7.75 (4
H, m), 7.88 (1H, m), 7.96 (1H, s), 7.98 (1H, d, J = 8Hz),
8.09 (1H, s), 8.23 (1H, d, J = 8Hz)
【０２１６】(7) １−（２−クロロベンジル）−３−ホ
ルミル−２−プロピル−Ｎ−（１Ｈ−テトラゾール−５
−イル）インドール−６−カルボキサミド mp : 275℃ (分解) NMR (DMSO-d6,δ) : 0.90 (3H,t,J=7Hz), 1.54 (2H,m),
3.13 (2H,t,J=7Hz),5.69 (2H,s), 6.38 (1H,d,J=8Hz),
7.19 (1H,t,J=8Hz), 7.33 (1H,t,J=8Hz), 7.60 (1H,d,
J=8Hz), 8.03 (1H,d,J=8Hz), 8.31 (1H,s), 8.32(1H,d,
J=8Hz), >10 (1H,s)(7) 1- (2-chlorobenzyl) -3-formyl-2-propyl-N- (1H-tetrazole-5
-Yl) indole-6-carboxamide mp: 275 ° C (decomposition) NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 7Hz), 1.54 (2H, m),
3.13 (2H, t, J = 7Hz), 5.69 (2H, s), 6.38 (1H, d, J = 8Hz),
7.19 (1H, t, J = 8Hz), 7.33 (1H, t, J = 8Hz), 7.60 (1H, d,
J = 8Hz), 8.03 (1H, d, J = 8Hz), 8.31 (1H, s), 8.32 (1H, d,
J = 8Hz),> 10 (1H, s)
【０２１７】製造例76 １−（２−クロロベンジル）−３−イソブチリル−２−
プロピルインドール−６−カルボン酸（100mg）のジメ
チルホルムアミド（３ml）溶液に、１−ヒドロキシベン
ゾトリアゾール（68mg）および１−（３−ジメチルアミ
ノプロピル）−３−エチルカルボジイミド塩酸塩（72m
g）を加え、混合物を20℃で一夜撹拌し、つぎに、ヒド
ロキシルアミン塩酸塩（35mg）およびジイソプロピルエ
チルアミン（0.088ml）を加えた。20℃で２時間撹拌
後、反応混合物を酢酸エチルと水とに分配する。有機層
を１Ｎ塩酸および食塩水で洗い、硫酸ナトリウムで乾燥
し、減圧下で蒸発させた。残留物を10％メタノール−ク
ロロホルム溶液を用いての分取薄層クロマトグラフィー
により精製し、酢酸エチルから再結晶して、１−（２−
クロロベンジル）−３−イソブチリル−２−プロピルイ
ンドール−６−カルボヒドロキサム酸（67mg）を淡赤色
結晶として得た。 mp : 185−186℃ NMR (CDCl3,δ) : 1.00 (3H,t,J=8Hz), 1.28 (6H,d,J=8
Hz), 1.60 (2H,sextet,J=8Hz), 3.02-3.06 (2H,m), 3.5
3 (2H,septet,J=8Hz), 5.47(2H,s), 6.20 (1H,dd,J=1,
8Hz), 7.03 (1H,t,J=8Hz), 7.20 (1H,t,J=8Hz), 7.46
(1H,d,J=8Hz), 7.57 (1H,d,J=8Hz), 7.77 (1H,s), 7.97
(1H,d,J=8Hz)Production Example 76 1- (2-Chlorobenzyl) -3-isobutyryl-2-
To a solution of propylindole-6-carboxylic acid (100 mg) in dimethylformamide (3 ml) was added 1-hydroxybenzotriazole (68 mg) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (72 m2).
g) was added and the mixture was stirred at 20 ° C. overnight, then hydroxylamine hydrochloride (35 mg) and diisopropylethylamine (0.088 ml) were added. After stirring at 20 ° C. for 2 hours, the reaction mixture is partitioned between ethyl acetate and water. The organic layer was washed with 1N hydrochloric acid and brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by preparative thin-layer chromatography using a 10% methanol-chloroform solution, recrystallized from ethyl acetate to give 1- (2-
(Chlorobenzyl) -3-isobutyryl-2-propylindole-6-carbohydroxamic acid (67 mg) was obtained as pale red crystals. mp: 185-186 ° C NMR (CDCl3 , δ): 1.00 (3H, t, J = 8Hz), 1.28 (6H, d, J = 8
Hz), 1.60 (2H, sextet, J = 8Hz), 3.02-3.06 (2H, m), 3.5
3 (2H, septet, J = 8Hz), 5.47 (2H, s), 6.20 (1H, dd, J = 1,
8Hz), 7.03 (1H, t, J = 8Hz), 7.20 (1H, t, J = 8Hz), 7.46
(1H, d, J = 8Hz), 7.57 (1H, d, J = 8Hz), 7.77 (1H, s), 7.97
(1H, d, J = 8Hz)
【０２１８】製造例77 製造例58で得た化合物（Ｉ−２）と適当なアミン（IV）
とを、製造例76と同様にして反応させて、下記(1)〜(2)
に記載の化合物を製造した。 (1) １−（２−クロロベンジル）−３−イソブチリル−
Ｏ−メチル−２−プロピルインドール−６−カルボヒド
ロキサム酸 NMR (CDCl3,δ) : 1.00 (3H,t,J=8Hz), 1.30 (6H,d,J=8
Hz), 1.54-1.66 (2H,m), 3.00-3.06 (2H,m), 3.53 (1H,
septet,J=8Hz), 3.86 (3H,s), 5.49(2H,s), 6.22 (1H,d
d,J=1, 8Hz), 7.03 (1H,dt,J=1, 8Hz), 7.23 (1H,dt,J=
1, 8Hz), 7.46 (1H,dd,J=1, 8Hz), 7.56 (1H,dd,J=1, 8
Hz), 7.75 (1H,d,J=1Hz), 7.96 (1H,d,J=8Hz), 8.82 (1
H,s) (2) １−（２−クロロベンジル）−３−イソブチル−２
−プロピル−Ｎ−（２−ピリジルメチル）インドール−
６−カルボキサミド NMR (CDCl3,δ) : 1.00 (3H,t,J=8Hz), 1.30 (6H,d,J=8
Hz), 1.62 (2H,sextet,J=8Hz), 3.03-3.07 (2H,m), 3.5
7 (1H,septet,J=8Hz), 4.66(2H,d,J=6Hz), 5.50 (2H,
s), 6.24 (1H,dd,J=1, 8Hz), 7.02 (1H,dt,J=1, 8Hz),
7.18-7.24 (2H,m), 7.33 (1H,d,J=8Hz), 7.45 (1H,d,J=
8Hz),7.62-7.68 (2H,m), 7.72 (1H,dd,J=1, 8Hz), 7.88
(1H,d,J=1Hz), 7.98(1H,d,J=8Hz), 8.56 (1H,d,J=6Hz)Production Example 77 Compound (I-2) obtained in Production Example 58 and a suitable amine (IV)
Were reacted in the same manner as in Production Example 76, and the following (1) to (2)
The compounds described in were prepared. (1) 1- (2-chlorobenzyl) -3-isobutyryl-
O-methyl-2-propylindole-6-carbohydroxamic acid NMR (CDCl3 , δ): 1.00 (3H, t, J = 8Hz), 1.30 (6H, d, J = 8
Hz), 1.54-1.66 (2H, m), 3.00-3.06 (2H, m), 3.53 (1H,
septet, J = 8Hz), 3.86 (3H, s), 5.49 (2H, s), 6.22 (1H, d
d, J = 1, 8Hz), 7.03 (1H, dt, J = 1, 8Hz), 7.23 (1H, dt, J =
1, 8Hz), 7.46 (1H, dd, J = 1, 8Hz), 7.56 (1H, dd, J = 1, 8
Hz), 7.75 (1H, d, J = 1Hz), 7.96 (1H, d, J = 8Hz), 8.82 (1
H, s) (2) 1- (2-chlorobenzyl) -3-isobutyl-2
-Propyl-N- (2-pyridylmethyl) indole-
6-carboxamide NMR (CDCl3 , δ): 1.00 (3H, t, J = 8Hz), 1.30 (6H, d, J = 8
Hz), 1.62 (2H, sextet, J = 8Hz), 3.03-3.07 (2H, m), 3.5
7 (1H, septet, J = 8Hz), 4.66 (2H, d, J = 6Hz), 5.50 (2H,
s), 6.24 (1H, dd, J = 1,8Hz), 7.02 (1H, dt, J = 1,8Hz),
7.18-7.24 (2H, m), 7.33 (1H, d, J = 8Hz), 7.45 (1H, d, J =
8Hz), 7.62-7.68 (2H, m), 7.72 (1H, dd, J = 1,8Hz), 7.88
(1H, d, J = 1Hz), 7.98 (1H, d, J = 8Hz), 8.56 (1H, d, J = 6Hz)
【０２１９】製造例78 製造例８−(2)で得た化合物（II）と適当なハロゲン化
物（III）とを、製造例54と同様にして反応させて、下
記(1)〜(2)に記載の化合物を製造した。 (1) １−（４−クロロ−２−フルオロベンジル）−３−
イソブチリル−２−プロピルインドール−６−カルボキ
サミド mp : 200−202℃ IR (KBr) : 3380, 3195, 1650, 1620 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.52-1.65 (2H,m), 3.06-3.10 (2H,m), 3.49-3.59
(1H,m), 5.47 (2H,s), 6.34 (1H,ddd,J=8, 8, 1Hz),
6.94 (1H,dd,J=8, 1Hz), 7.19 (1H,d,J=8Hz), 7.60 (1
H,d,J=8Hz), 7.89 (1H,s), 7.97 (1H,d,J=8Hz) MASS (m/z) : 415 (M++1), 76 (bp) (2) ３−イソブチリル−（２−メトキシカルボニルベン
ジル）−２−プロピルインドール−６−カルボキサミド mp : 170−172℃ IR (KBr) : 3420, 1720, 1650 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.33 (6H,d,J=7
Hz), 1.56-1.69 (2H,m), 3.00-3.06 (2H,m), 3.54-3.63
(1H,m), 4.02 (3H,s), 5.91 (2H,s),6.69 (1H,d,J=7.5
Hz), 7.24-7.36 (1H,m), 7.63 (1H,dd,J=8, 1Hz),7.80
(1H,s), 7.99 (1H,d,J=8Hz), 8.12-8.16 (1H,m) MASS (m/z) : 421 (M++1)Production Example 78 The compound (II) obtained in Production Example 8- (2) was reacted with an appropriate halide (III) in the same manner as in Production Example 54 to obtain the following (1) to (2) The compounds described in were prepared. (1) 1- (4-chloro-2-fluorobenzyl) -3-
Isobutyryl-2-propylindole-6-carboxamide mp: 200-202 ° C IR (KBr): 3380, 3195, 1650, 1620 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.52-1.65 (2H, m), 3.06-3.10 (2H, m), 3.49-3.59
(1H, m), 5.47 (2H, s), 6.34 (1H, ddd, J = 8, 8, 1Hz),
6.94 (1H, dd, J = 8,1Hz), 7.19 (1H, d, J = 8Hz), 7.60 (1
H, d, J = 8Hz), 7.89 (1H, s), 7.97 (1H, d, J = 8Hz) MASS (m / z): 415 (M+ +1), 76 (bp) (2) 3- Isobutyryl- (2-methoxycarbonylbenzyl) -2-propylindole-6-carboxamide mp: 170-172 ° C IR (KBr): 3420, 1720, 1650 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t) , J = 7Hz), 1.33 (6H, d, J = 7
Hz), 1.56-1.69 (2H, m), 3.00-3.06 (2H, m), 3.54-3.63
(1H, m), 4.02 (3H, s), 5.91 (2H, s), 6.69 (1H, d, J = 7.5
Hz), 7.24-7.36 (1H, m), 7.63 (1H, dd, J = 8,1Hz), 7.80
(1H, s), 7.99 (1H, d, J = 8Hz), 8.12-8.16 (1H, m) MASS (m / z): 421 (M+ +1)
【０２２０】製造例79 ３−イソブチリル−２−プロピルインドール−６−カル
ボキサミド(100mg)、臭化４−クロロベンジル（113mg）
および炭酸カリウム（152mg）のジメチルホルムアミド
（２ml）中混合物を、60℃で２時間加熱し、酢酸エチル
と水とに分配した。有機層を水および食塩水で洗い、硫
酸マグネシウムで乾燥した。溶媒を蒸発させ、残留物を
酢酸エチル−ヘキサン混合物から結晶化させた。粗結晶
を酢酸エチル−ヘキサン混合物から再結晶して、１−
（４−クロロベンジル）−３−イソブチリル−２−プロ
ピルインドール−６−カルボキサミド（97mg）を無色結
晶として得た。 mp : 183−184℃ NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.50-1.64 (2H,m), 3.06-3.12 (2H,m), 3.55 (2H,
septet,J=7Hz), 5.42 (2H,s), 6.87(2H,d,J=8Hz), 7.25
(2H,d,J=8Hz), 7.60 (1H,dd,J=1, 8Hz), 7.87 (1H,d,J
=1Hz), 7.95 (1H,d,J=8Hz)Production Example 79 3-Isobutyryl-2-propylindole-6-carboxamide (100 mg), 4-chlorobenzyl bromide (113 mg)
And a mixture of potassium carbonate (152 mg) in dimethylformamide (2 ml) was heated at 60 ° C. for 2 hours and partitioned between ethyl acetate and water. The organic layer was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated and the residue was crystallized from an ethyl acetate-hexane mixture. The crude crystals were recrystallized from an ethyl acetate-hexane mixture to give 1-
(4-Chlorobenzyl) -3-isobutyryl-2-propylindole-6-carboxamide (97 mg) was obtained as colorless crystals. mp: 183-184 ° C NMR (CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.29 (6H, d, J = 7
Hz), 1.50-1.64 (2H, m), 3.06-3.12 (2H, m), 3.55 (2H,
septet, J = 7Hz), 5.42 (2H, s), 6.87 (2H, d, J = 8Hz), 7.25
(2H, d, J = 8Hz), 7.60 (1H, dd, J = 1,8Hz), 7.87 (1H, d, J
= 1Hz), 7.95 (1H, d, J = 8Hz)
【０２２１】製造例80 製造例８−(2)または製造例15−(3)で得た化合物（II）
と適当なハロゲン化物（III）とを、製造例79と同様に
して反応させて、下記(1)〜(8)に記載の化合物を製造し
た。 (1) １−ベンジル−３−イソブチリル−２−プロピルイ
ンドール−６−カルボキサミド mp : 164−166℃ NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.60 (2H,sextet,J=7Hz), 3.09-3.13 (2H,m), 3.5
5 (2H,septet,J=7Hz), 5.46(2H,s), 6.96-6.98 (2H,m),
7.24-7.32 (2H,m), 7.61 (1H,d,J=8Hz),7.91 (1H,s),
7.95 (1H,d,J=8Hz) (2) １−（３−クロロベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボキサミド mp : 164−166℃ NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.50-1.65 (2H,m), 3.06-3.12 (2H,m), 3.55 (2H,
septet,J=7Hz), 5.42 (2H,s), 6.78(1H,dd,J=1, 8Hz),
6.96 (1H,d,J=1Hz), 7.18-7.27 (2H,m), 7.60 (1H,d,J=
8Hz), 7.88 (1H,s), 7.95 (1H,d,J=8Hz)Production Example 80 Compound (II) obtained in Production Example 8- (2) or Production Example 15- (3)
And a suitable halide (III) were reacted in the same manner as in Production Example 79 to produce the following compounds (1) to (8). (1) 1-benzyl-3-isobutyryl-2-propylindole-6-carboxamide mp: 164-166 ° C NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.29 (6H, d, J = 7
Hz), 1.60 (2H, sextet, J = 7Hz), 3.09-3.13 (2H, m), 3.5
5 (2H, septet, J = 7Hz), 5.46 (2H, s), 6.96-6.98 (2H, m),
7.24-7.32 (2H, m), 7.61 (1H, d, J = 8Hz), 7.91 (1H, s),
7.95 (1H, d, J = 8Hz) (2) 1- (3-chlorobenzyl) -3-isobutyryl-
2-propylindole-6-carboxamide mp: 164-166 ° C NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.50-1.65 (2H, m), 3.06-3.12 (2H, m), 3.55 (2H,
septet, J = 7Hz), 5.42 (2H, s), 6.78 (1H, dd, J = 1,8Hz),
6.96 (1H, d, J = 1Hz), 7.18-7.27 (2H, m), 7.60 (1H, d, J =
8Hz), 7.88 (1H, s), 7.95 (1H, d, J = 8Hz)
【０２２２】(3) ３−イソブチリル−２−プロピル−１
−（２−トリフルオロメチルベンジル）インドール−６
−カルボキサミド mp : 86−87℃ NMR (CDCl3,δ) : 0.99 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.52-1.65 (2H,m), 2.98-3.04 (2H,m), 3.56 (2H,
septet,J=7Hz), 5.62 (2H,s), 6.33(1H,d,J=8Hz), 7.30
(1H,t,J=1Hz), 7.38 (1H,t,J=1Hz), 7.64 (1H,d,J=8H
z), 7.75 (1H,d,J=8Hz), 7.84 (1H,s), 7.98 (1H,d,J=8
Hz) (4) ３−イソブチリル−１−（２−フェニルベンジル）
−２−プロピルインドール−６−カルボキサミド mp : 162−164℃ NMR (CDCl3,δ) : 0.89 (3H,t,J=7Hz), 1.27 (6H,d,J=7
Hz), 1.36-1.50 (2H,m), 2.90-2.96 (2H,m), 3.53 (2H,
septet,J=7Hz), 5.32 (2H,s), 6.48(1H,d,J=8Hz), 7.10
-7.16 (1H,m), 7.30-7.34 (2H,m), 7.42-7.84 (3H,m),
7.52-7.55 (2H,m), 7.60 (1H,d,J=8Hz), 7.84 (1H,s),
7.93 (1H,d,J=8Hz)(3) 3-isobutyryl-2-propyl-1
-(2-trifluoromethylbenzyl) indole-6
-Carboxamide mp: 86-87 ° C NMR (CDCl3 , δ): 0.99 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.52-1.65 (2H, m), 2.98-3.04 (2H, m), 3.56 (2H, m
(septet, J = 7Hz), 5.62 (2H, s), 6.33 (1H, d, J = 8Hz), 7.30
(1H, t, J = 1Hz), 7.38 (1H, t, J = 1Hz), 7.64 (1H, d, J = 8H
z), 7.75 (1H, d, J = 8Hz), 7.84 (1H, s), 7.98 (1H, d, J = 8
Hz) (4) 3-isobutyryl-1- (2-phenylbenzyl)
-2-propylindole-6-carboxamide mp: 162-164 ° C NMR (CDCl3 , δ): 0.89 (3H, t, J = 7Hz), 1.27 (6H, d, J = 7
Hz), 1.36-1.50 (2H, m), 2.90-2.96 (2H, m), 3.53 (2H,
(septet, J = 7Hz), 5.32 (2H, s), 6.48 (1H, d, J = 8Hz), 7.10
-7.16 (1H, m), 7.30-7.34 (2H, m), 7.42-7.84 (3H, m),
7.52-7.55 (2H, m), 7.60 (1H, d, J = 8Hz), 7.84 (1H, s),
7.93 (1H, d, J = 8Hz)
【０２２３】(5) １−［（５−クロロ−２−チエニル）
メチル］−３−イソブチリル−２−プロピルインドール
−６−カルボキサミド mp : 178−180℃ NMR (CDCl3,δ) : 1.07 (3H,t,J=7Hz), 1.27 (6H,d,J=7
Hz), 1.65 (2H,sextet,J=7Hz), 3.15-3.20 (2H,m), 3.5
4 (2H,septet,J=7Hz), 5.46(2H,s), 6.59 (1H,d,J=2H
z), 6.72 (2H,d,J=2Hz), 7.60 (1H,d,J=8Hz),7.92 (1H,
d,J=8Hz), 8.04 (1H,s) (6) ３−イソブチリル−１−フェネチル−２−プロピル
インドール−６−カルボキサミド mp : 180−181℃ NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.26 (6H,d,J=7
Hz), 1.61 (2H,septet,J=7Hz), 2.88-2.92 (2H,m), 3.1
0 (2H,t,J=7Hz), 3.52 (2H,septet,J=7Hz), 4.42 (2H,
t,J=7Hz), 7.05-7.09 (2H,m), 7.22-7.32(3H,m), 7.52
(1H,d,J=8Hz), 7.92 (1H,d,J=8Hz), 7.96 (1H,s)(5) 1-[(5-chloro-2-thienyl)
Methyl] -3-isobutyryl-2-propylindole-6-carboxamide mp: 178-180 ° C NMR (CDCl3 , δ): 1.07 (3H, t, J = 7Hz), 1.27 (6H, d, J = 7
Hz), 1.65 (2H, sextet, J = 7Hz), 3.15-3.20 (2H, m), 3.5
4 (2H, septet, J = 7Hz), 5.46 (2H, s), 6.59 (1H, d, J = 2H
z), 6.72 (2H, d, J = 2Hz), 7.60 (1H, d, J = 8Hz), 7.92 (1H,
d, J = 8Hz), 8.04 (1H, s) (6) 3-isobutyryl-1-phenethyl-2-propylindole-6-carboxamide mp: 180-181 ° C NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.26 (6H, d, J = 7
Hz), 1.61 (2H, septet, J = 7Hz), 2.88-2.92 (2H, m), 3.1
0 (2H, t, J = 7Hz), 3.52 (2H, septet, J = 7Hz), 4.42 (2H,
t, J = 7Hz), 7.05-7.09 (2H, m), 7.22-7.32 (3H, m), 7.52
(1H, d, J = 8Hz), 7.92 (1H, d, J = 8Hz), 7.96 (1H, s)
【０２２４】(7) １−（２−クロロベンジル）−３−メ
トキシアセチル−２−プロピルインドール−６−カルボ
キサミド mp : 165−167℃ NMR (DMSO-d6,δ) : 0.92 (3H,t,J=8Hz), 1.46 (2H,sex
tet,J=8Hz), 3.01-3.05 (2H,m), 3.42 (3H,s), 4.68 (2
H,s), 5.62 (2H,s), 6.22 (1H,d,J=8Hz), 7.16 (1H,t,J
=8Hz), 7.28 (1H,br s), 7.32 (1H,t,J=8Hz),7.56 (1H,
d,J=8Hz), 7.92 (1H,d,J=8Hz), 7.93 (1H,br s), 8.01
(1H,s) (8) １−（６−クロロ−３,４−メチレンジオキシベン
ジル）−３−メトキシアセチル−２−プロピルインドー
ル−６−カルボキサミド mp : 204−206℃ NMR (DMSO-d6,δ) : 0.95 (3H,t,J=8Hz), 1.50 (2H,sex
tet,J=8Hz), 3.02-3.06 (2H,m), 3.40 (3H,s), 4.70 (2
H,s), 5.51 (1H,s), 5.98 (2H,s),7.23 (1H,s), 7.32
(1H,br s), 7.80 (1H,d,J=8Hz), 7.93 (1H,d,J=8Hz),7.
96 (1H,br s), 8.02 (1H,s)(7) 1- (2-chlorobenzyl) -3-methoxyacetyl-2-propylindole-6-carboxamide mp: 165-167 ° C NMR (DMSO-d6 , δ): 0.92 (3H, t, J = 8Hz), 1.46 (2H, sex
tet, J = 8Hz), 3.01-3.05 (2H, m), 3.42 (3H, s), 4.68 (2
H, s), 5.62 (2H, s), 6.22 (1H, d, J = 8Hz), 7.16 (1H, t, J
= 8Hz), 7.28 (1H, brs), 7.32 (1H, t, J = 8Hz), 7.56 (1H, br
d, J = 8Hz), 7.92 (1H, d, J = 8Hz), 7.93 (1H, br s), 8.01
(1H, s) (8) 1- (6-chloro-3,4-methylenedioxybenzyl) -3-methoxyacetyl-2-propylindole-6-carboxamide mp: 204-206 ° C NMR (DMSO-d6 , δ): 0.95 (3H, t, J = 8Hz), 1.50 (2H, sex
tet, J = 8Hz), 3.02-3.06 (2H, m), 3.40 (3H, s), 4.70 (2
H, s), 5.51 (1H, s), 5.98 (2H, s), 7.23 (1H, s), 7.32
(1H, brs), 7.80 (1H, d, J = 8Hz), 7.93 (1H, d, J = 8Hz), 7.
96 (1H, brs), 8.02 (1H, s)
【０２２５】製造例81 製造例２、製造例６−(1)、製造例９、製造例10、製造
例12、製造例13−(4)または製造例14−(5)で得た化合物
（II）と適当なハロゲン化物（III）とを、製造例54と
同様にして反応させて、下記(1)〜(16)に記載の化合物
を製造した。 (1) １−（２−フルオロベンジル）−３−イソブチリル
−２−プロピルインドール−６−カルボン酸メチルエス
テル mp : 120−121.5℃ IR (KBr) : 1710, 1700, 1660 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.55-1.64 (2H,m), 3.06-3.12 (2H,m), 3.51-3.61
(1H,m), 3.92 (3H,s), 5.50 (2H,s),6.43 (1H,t,J=7.5
Hz), 6.95 (1H,t,J=7Hz), 7.10-7.17 (1H,m), 7.22-7.2
8 (1H,m), 7.95 (2H,s), 8.02 (1H,s) MASS (m/z) : 396 (M++1), 76 (bp) (2) １−（２−ブロモベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボン酸メチルエステ
ル mp : 90−92℃ IR (KBr) : 1705, 1650 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.56-1.67 (2H,m), 3.04 (2H,t,J=7Hz), 3.52-3.6
1 (1H,m), 3.93 (3H,s), 5.47 (2H,s),6.20 (1H,t,J=7.
5Hz), 7.06-7.18 (2H,m), 7.65 (1H,t,J=7.5Hz), 7.95
(1H,s), 7.97 (2H,s) MASS (m/z) : 458 (M++1+2), 458 (M++1), 76 (bp)Preparation Example 81 The compound obtained in Preparation Example 2, Preparation Example 6- (1), Preparation Example 9, Preparation Example 10, Preparation Example 12, Preparation Example 13- (4) or Preparation Example 14- (5) II) and an appropriate halide (III) were reacted in the same manner as in Production Example 54 to produce the following compounds (1) to (16). (1) 1- (2-Fluorobenzyl) -3-isobutyryl-2-propylindole-6-carboxylic acid methyl ester mp: 120-121.5 ° C IR (KBr): 1710, 1700, 1660 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.29 (6H, d, J = 7
Hz), 1.55-1.64 (2H, m), 3.06-3.12 (2H, m), 3.51-3.61
(1H, m), 3.92 (3H, s), 5.50 (2H, s), 6.43 (1H, t, J = 7.5
Hz), 6.95 (1H, t, J = 7Hz), 7.10-7.17 (1H, m), 7.22-7.2
8 (1H, m), 7.95 (2H, s), 8.02 (1H, s) MASS (m / z): 396 (M+ +1), 76 (bp) (2) 1- (2-bromobenzyl) -3-isobutyryl-
2-propylindole-6-carboxylic acid methyl ester mp: 90-92 ° C IR (KBr): 1705, 1650 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.30 (6H , d, J = 7
Hz), 1.56-1.67 (2H, m), 3.04 (2H, t, J = 7Hz), 3.52-3.6
1 (1H, m), 3.93 (3H, s), 5.47 (2H, s), 6.20 (1H, t, J = 7.
5Hz), 7.06-7.18 (2H, m), 7.65 (1H, t, J = 7.5Hz), 7.95
(1H, s), 7.97 (2H, s) MASS (m / z): 458 (M+ +1 +2), 458 (M+ +1), 76 (bp)
【０２２６】(3) １−（２−ヨードベンジル）−３−イ
ソブチリル−２−プロピルインドール−６−カルボン酸
メチルエステル IR (KBr) : 1710, 1650, 1430 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.53-1.67 (2H,m), 2.98-3.05 (2H,m), 3.53-3.62
(1H,m), 3.93 (3H,s), 5.37 (2H,s),6.16 (1H,t,J=7.5
Hz), 6.99 (1H,t,J=7.5Hz), 7.12 (1H,t,J=7.5Hz),7.90
-7.97 (4H,m) MASS (m/z) : 504 (M++1) (4) ３−イソブチリル−１−（２−メチルベンジル）−
２−プロピルインドール−６−カルボン酸メチルエステ
ル mp : 99−102℃ IR (KBr) : 1705, 1650, 1285 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.54-1.69 (2H,m), 2.50 (3H,s), 3.00-3.06 (2H,
m), 3.51-3.65 (1H,m), 3.89 (3H,s),5.39 (2H,s), 6.1
7 (1H,t,J=7.5Hz), 6.98 (1H,t,J=7.5Hz), 7.18 (1H,t,
J=7.5Hz), 7.25 (1H,d,J=7.5Hz), 7.92 (1H,s), 7.96
(2H,s) MASS (m/z) : 392 (M++1)(3) 1- (2-Iodobenzyl) -3-isobutyryl-2-propylindole-6-carboxylic acid methyl ester IR (KBr): 1710, 1650, 1430 cm-1 NMR (CDCl3 , δ) : 1.03 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.53-1.67 (2H, m), 2.98-3.05 (2H, m), 3.53-3.62
(1H, m), 3.93 (3H, s), 5.37 (2H, s), 6.16 (1H, t, J = 7.5
Hz), 6.99 (1H, t, J = 7.5Hz), 7.12 (1H, t, J = 7.5Hz), 7.90
-7.97 (4H, m) MASS (m / z): 504 (M+ +1) (4) 3-isobutyryl-1- (2-methylbenzyl)-
2-propylindole-6-carboxylic acid methyl ester mp: 99-102 ° C IR (KBr): 1705, 1650, 1285 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.54-1.69 (2H, m), 2.50 (3H, s), 3.00-3.06 (2H,
m), 3.51-3.65 (1H, m), 3.89 (3H, s), 5.39 (2H, s), 6.1
7 (1H, t, J = 7.5Hz), 6.98 (1H, t, J = 7.5Hz), 7.18 (1H, t, J
J = 7.5Hz), 7.25 (1H, d, J = 7.5Hz), 7.92 (1H, s), 7.96
(2H, s) MASS (m / z): 392 (M+ +1)
【０２２７】(5) ３−イソブチリル−１−（２−メトキ
シベンジル）−２−プロピルインドール−６−カルボン
酸メチルエステル mp : 103−105℃ IR (KBr) : 1710, 1650 cm-1 NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.56-1.68 (2H,m), 3.05-3.10 (2H,m), 3.53-3.62
(1H,m), 3.90 (3H,s), 3.98 (3H,s),5.44 (2H,s), 6.2
7 (1H,d,J=7.5Hz), 6.74 (1H,t,J=7.5Hz), 6.94 (1H,d,
J=7.5Hz), 7.25 (1H,t,J=7.5Hz), 7.95 (2H,s), 8.00
(1H,d,J=7.5Hz) MASS (m/z) : 408 (M++1), 76 (bp) (6) １−（２−シアノベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボン酸メチルエステ
ル mp : 159−161℃ IR (KBr) : 2220, 1730, 1660 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.52-1.65 (2H,m), 3.03-3.08 (2H,m), 3.53-3.60
(1H,m), 3.92 (3H,s), 5.66 (2H,s),6.44-6.49 (1H,
m), 7.38-7.43 (2H,m), 7.76-7.80 (1H,m), 7.95 (1H,
s),7.98 (2H,s) MASS (m/z) : 403 (M++1), 76 (bp)(5) 3-isobutyryl-1- (2-methoxybenzyl) -2-propylindole-6-carboxylic acid methyl ester mp: 103-105 ° C IR (KBr): 1710, 1650 cm-1 NMR (CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.56-1.68 (2H, m), 3.05-3.10 (2H, m), 3.53-3.62
(1H, m), 3.90 (3H, s), 3.98 (3H, s), 5.44 (2H, s), 6.2
7 (1H, d, J = 7.5Hz), 6.74 (1H, t, J = 7.5Hz), 6.94 (1H, d,
J = 7.5Hz), 7.25 (1H, t, J = 7.5Hz), 7.95 (2H, s), 8.00
(1H, d, J = 7.5Hz) MASS (m / z): 408 (M+ +1), 76 (bp) (6) 1- (2-cyanobenzyl) -3-isobutyryl-
2-propylindole-6-carboxylic acid methyl ester mp: 159-161 ° C IR (KBr): 2220, 1730, 1660 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.52-1.65 (2H, m), 3.03-3.08 (2H, m), 3.53-3.60
(1H, m), 3.92 (3H, s), 5.66 (2H, s), 6.44-6.49 (1H,
m), 7.38-7.43 (2H, m), 7.76-7.80 (1H, m), 7.95 (1H,
s), 7.98 (2H, s) MASS (m / z): 403 (M+ +1), 76 (bp)
【０２２８】(7) ３−イソブチリル−１−（２−ニトロ
ベンジル）−２−プロピルインドール−６−カルボン酸
メチルエステル mp : 165.5−166.5℃ IR (KBr) : 1705, 1650, 1530, 1520 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 1.56-1.65 (2H,m), 3.03 (2H,t,J=7Hz), 3.54-3.6
5 (1H,m), 3.90 (3H,s), 5.89 (2H,s),6.27 (1H,d,J=7.
5Hz), 7.40-7.51 (2H,m), 7.89 (1H,s), 8.00 (2H,s),
8.30 (1H,d,J=7.5Hz) MASS (m/z) : 423 (M++1), 76 (bp) (8) １−（２,６−ジクロロベンジル）−３−イソブチ
リル−２−プロピルインドール−６−カルボン酸メチル
エステル mp : 129.5−132℃ IR (KBr) : 1710, 1660, 1430 cm-1 NMR (CDCl3,δ) : 0.96 (3H,t,J=7Hz), 1.27 (6H,d,J=7
Hz), 1.38-1.50 (2H,m), 3.15-3.20 (2H,m), 3.47-3.60
(1H,m), 3.92 (3H,s), 5.70 (2H,s),7.17-7.39 (3H,
m), 7.88 (2H,s), 8.03 (1H,s) MASS (m/z) : 446 (M++1)(7) 3-isobutyryl-1- (2-nitrobenzyl) -2-propylindole-6-carboxylic acid methyl ester mp: 165.5-166.5 ° C. IR (KBr): 1705, 1650, 1530, 1520 cm− 1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.31 (6H, d, J = 7
Hz), 1.56-1.65 (2H, m), 3.03 (2H, t, J = 7Hz), 3.54-3.6
5 (1H, m), 3.90 (3H, s), 5.89 (2H, s), 6.27 (1H, d, J = 7.
5Hz), 7.40-7.51 (2H, m), 7.89 (1H, s), 8.00 (2H, s),
8.30 (1H, d, J = 7.5 Hz) MASS (m / z): 423 (M++ 1), 76 (bp) (8) 1- (2,6-dichlorobenzyl) -3-isobutyryl-2- Propylindole-6-carboxylic acid methyl ester mp: 129.5-132 ° C IR (KBr): 1710, 1660, 1430 cm-1 NMR (CDCl3 , δ): 0.96 (3H, t, J = 7Hz), 1.27 (6H , d, J = 7
Hz), 1.38-1.50 (2H, m), 3.15-3.20 (2H, m), 3.47-3.60
(1H, m), 3.92 (3H, s), 5.70 (2H, s), 7.17-7.39 (3H,
m), 7.88 (2H, s), 8.03 (1H, s) MASS (m / z): 446 (M+ +1)
【０２２９】(9) １−（２−クロロ−４−フルオロベン
ジル）−３−イソブチリル−２−プロピルインドール−
６−カルボン酸メチルエステル mp : 140−141℃ IR (KBr) : 1705, 1649, 1488, 1279 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.40 (6H,d,J=7
Hz), 1.52-1.66 (2H,m), 3.01-3.06 (2H,m), 3.52-3.60
(1H,m), 3.93 (3H,s), 5.48 (2H,s),6.20-6.25 (1H,
m), 6.79 (1H,ddd,J=7.5, 7.5, 1Hz), 7.21-7.25 (1H,
m), 7.94 (1H,s), 7.97 (2H,s) MASS (m/z) : 430 (M++1), 76 (bp) (10) １−（４−ブロモ−２−フルオロベンジル）−３
−イソブチリル−２−プロピルインドール−６−カルボ
ン酸メチルエステル mp : 110−111.5℃ IR (KBr) : 1705, 1649, 1488, 1279 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.53-1.65 (2H,m), 3.05-3.10 (2H,m), 3.51-3.60
(1H,m), 3.94 (3H,s), 5.44 (2H,s),6.28 (1H,t,J=7.5
Hz), 7.10 (1H,dd,J=7.5, 1Hz), 7.35 (1H,d,J=7.5Hz),
7.96 (1H,s) MASS (m/z) : 476 (M++1), 474 (M+), 76 (bp)(9) 1- (2-chloro-4-fluorobenzyl) -3-isobutyryl-2-propylindole-
6-Carboxylic acid methyl ester mp: 140-141 ° C IR (KBr): 1705, 1649, 1488, 1279 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.40 (6H, d, J = 7
Hz), 1.52-1.66 (2H, m), 3.01-3.06 (2H, m), 3.52-3.60
(1H, m), 3.93 (3H, s), 5.48 (2H, s), 6.20-6.25 (1H,
m), 6.79 (1H, ddd, J = 7.5, 7.5, 1Hz), 7.21-7.25 (1H,
m), 7.94 (1H, s), 7.97 (2H, s) MASS (m / z): 430 (M++ 1), 76 (bp) (10) 1- (4-bromo-2-fluorobenzyl) -3
-Isobutyryl-2-propylindole-6-carboxylic acid methyl ester mp: 110-111.5 ° C IR (KBr): 1705, 1649, 1488, 1279 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.29 (6H, d, J = 7
Hz), 1.53-1.65 (2H, m), 3.05-3.10 (2H, m), 3.51-3.60
(1H, m), 3.94 (3H, s), 5.44 (2H, s), 6.28 (1H, t, J = 7.5
Hz), 7.10 (1H, dd, J = 7.5,1Hz), 7.35 (1H, d, J = 7.5Hz),
7.96 (1H, s) MASS (m / z): 476 (M+ +1), 474 (M+ ), 76 (bp)
【０２３０】(11) ３−ベンゾイル−１−（２−クロロ
ベンジル）−２−プロピルインドール−６−カルボン酸
メチルエステル NMR (CDCl3,δ) : 0.94 (3H,t,J=8Hz), 1.56-1.70 (2H,
m), 2.93-2.98 (2H,m), 3.87 (3H,s), 5.55 (2H,s), 6.
33 (1H,ddd,J=1, 8Hz), 7.08 (1H,dt,J=1, 8Hz), 7.21
(1H,d,J=8Hz), 7.22-7.28 (1H,m), 7.46-7.52 (3H,m),
7.57-7.63 (1H,m), 7.72-7.82 (3H,m), 7.93 (1H,d,J=1
Hz) (12) １−（２−クロロベンジル）−３−シアノ−２−
プロピルインドール−６−カルボン酸メチルエステル mp : 132−133℃ IR (KBr) : 2215, 1709, 1284 cm-1 NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.70 (2H,sexte
t,J=7Hz), 2.89 (2H,t,J=7.5Hz), 3.92 (3H,s), 5.49
(2H,s), 6.24 (1H,d,J=7.5Hz), 7.08(1H,t,J=7.5Hz),
7.22-7.28 (1H,m), 7.47 (1H,d,J=7.5Hz), 7.77 (1H,d,
J=7.5Hz), 7.95-8.00 (2H,m) MASS (m/z) : 367 (M++1), 76 (bp)(11) 3-benzoyl-1- (2-chlorobenzyl) -2-propylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 0.94 (3H, t, J = 8 Hz), 1.56 -1.70 (2H,
m), 2.93-2.98 (2H, m), 3.87 (3H, s), 5.55 (2H, s), 6.
33 (1H, ddd, J = 1,8Hz), 7.08 (1H, dt, J = 1,8Hz), 7.21
(1H, d, J = 8Hz), 7.22-7.28 (1H, m), 7.46-7.52 (3H, m),
7.57-7.63 (1H, m), 7.72-7.82 (3H, m), 7.93 (1H, d, J = 1
Hz) (12) 1- (2-chlorobenzyl) -3-cyano-2-
Methyl propylindole-6-carboxylate mp: 132-133 ° C IR (KBr): 2215, 1709, 1284 cm-1 NMR (CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.70 (2H , sexte
(t, J = 7Hz), 2.89 (2H, t, J = 7.5Hz), 3.92 (3H, s), 5.49
(2H, s), 6.24 (1H, d, J = 7.5Hz), 7.08 (1H, t, J = 7.5Hz),
7.22-7.28 (1H, m), 7.47 (1H, d, J = 7.5Hz), 7.77 (1H, d,
J = 7.5Hz), 7.95-8.00 (2H, m) MASS (m / z): 367 (M+ +1), 76 (bp)
【０２３１】(13) １−（２−クロロベンジル）−２−
エチル−３−イソブチリルインドール−６−カルボン酸
メチルエステル NMR (CDCl3,δ) : 1.22 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 3.08 (2H,q,J=7Hz), 3.56 (1H,m), 3.91 (3H,s),
5.50 (2H,s), 6.23 (1H,d,J=8Hz),7.04 (1H,t,J=8Hz),
7.22 (1H,t,J=8Hz), 7.46 (1H,d,J=8Hz), 7.93-7.98(3
H,m) (14) １−（２−クロロベンジル）−３−イソブチリル
−２−メチルインドール−６−カルボン酸メチルエステ
ル NMR (CDCl3,δ) : 1.32 (6H,d,J=7Hz), 2.71 (3H,s),
3.56 (1H,m), 3.92(3H,s), 5.52 (2H,s), 6.24 (1H,d,J
=8Hz), 7.05 (1H,t,J=8Hz), 7.23(1H,t,J=8Hz), 7.46
(1H,d,J=8Hz), 7.92-8.05 (3H,m)(13) 1- (2-chlorobenzyl) -2-
Ethyl-3-isobutyrylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.22 (3H, t, J = 7 Hz), 1.31 (6H, d, J = 7)
Hz), 3.08 (2H, q, J = 7Hz), 3.56 (1H, m), 3.91 (3H, s),
5.50 (2H, s), 6.23 (1H, d, J = 8Hz), 7.04 (1H, t, J = 8Hz),
7.22 (1H, t, J = 8Hz), 7.46 (1H, d, J = 8Hz), 7.93-7.98 (3
H, m) (14) 1- (2- chlorobenzyl) -3-isobutyryl-2-methyl-indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.32 (6H, d, J = 7Hz), 2.71 (3H, s),
3.56 (1H, m), 3.92 (3H, s), 5.52 (2H, s), 6.24 (1H, d, J
= 8Hz), 7.05 (1H, t, J = 8Hz), 7.23 (1H, t, J = 8Hz), 7.46
(1H, d, J = 8Hz), 7.92-8.05 (3H, m)
【０２３２】(15) １−（２−クロロベンジル）−３−
イソブチリル−２−メトキシメチルインドール−６−カ
ルボン酸メチルエステル NMR (CDCl3,δ) : 1.29 (6H,d,J=7Hz), 3.31 (3H,s),
3.55 (1H,m), 3.89(3H,s), 4.91 (2H,s), 5.63 (2H,s),
6.23 (1H,d,J=8Hz), 7.02 (1H,t,J=8Hz), 7.19 (1H,t,
J=8Hz), 7.44 (1H,d,J=8Hz), 7.95-8.02 (3H,m) (16) １−（２−クロロベンジル）−３−イソブチリル
インドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.26 (6H,d,J=7Hz), 3.28 (1H,m),
3.93 (3H,s), 5.52(2H,s), 6.77 (1H,d,J=8Hz), 7.18
(1H,t,J=8Hz), 7.29 (1H,t,J=8Hz),7.48 (1H,d,J=8Hz),
7.89 (1H,s), 8.02 (1H,d,J=8Hz), 8.10 (1H,s),8.49
(1H,d,J=8Hz)(15) 1- (2-chlorobenzyl) -3-
Isobutyryl-2-methoxymethyl-indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.29 (6H, d, J = 7Hz), 3.31 (3H, s),
3.55 (1H, m), 3.89 (3H, s), 4.91 (2H, s), 5.63 (2H, s),
6.23 (1H, d, J = 8Hz), 7.02 (1H, t, J = 8Hz), 7.19 (1H, t,
J = 8Hz), 7.44 (1H, d, J = 8Hz), 7.95-8.02 (3H, m) (16) 1- (2-chlorobenzyl) -3-isobutyrylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.26 (6H, d, J = 7Hz), 3.28 (1H, m),
3.93 (3H, s), 5.52 (2H, s), 6.77 (1H, d, J = 8Hz), 7.18
(1H, t, J = 8Hz), 7.29 (1H, t, J = 8Hz), 7.48 (1H, d, J = 8Hz),
7.89 (1H, s), 8.02 (1H, d, J = 8Hz), 8.10 (1H, s), 8.49
(1H, d, J = 8Hz)
【０２３３】製造例82 製造例１−(5)および製造例２で得た化合物（II）か
ら、製造例79と同様にして、下記(1)〜(2)に記載の化合
物を製造した。 (1) ３−イソブチリル−２−プロピル−１−（２−ピリ
ジルメチル）インドール−６−カルボン酸メチルエステ
ル NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.60 (2H,sextet,J=7Hz), 3.12-3.16 (2H,m), 3.5
6 (2H,septet,J=7Hz), 3.90(3H,s), 5.58 (2H,s), 6.58
(1H,d,J=8Hz), 7.22 (1H,dd,J=5, 8Hz),7.55 (1H,dt,J
=1, 8Hz), 7.94 (2H,s), 8.02 (1H,s), 8.63 (1H,dd,J=
1, 5Hz) (2) ３−アセチル−１−（６−クロロ−３,４−メチレ
ンジオキシベンジル）−２−プロピルインドール−６−
カルボン酸メチルエステル mp : 210−212℃ NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.63 (2H,sexte
t,J=7Hz), 2.37(3H,s), 3.04-3.08 (2H,m), 3.92 (3H,
s), 5.40 (2H,s), 5.70 (1H,s),5.90 (2H,s), 6.92 (1
H,s), 7.95 (1H,s), 7.97 (1H,d,J=8Hz), 8.04(1H,d,J=
8Hz)Production Example 82 From the compound (II) obtained in Production Example 1- (5) and Production Example 2, the following compounds (1) and (2) were produced in the same manner as in Production Example 79. (1) 3-isobutyryl-2-propyl-1- (2-pyridylmethyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.01 (3H, t, J = 7 Hz), 1.30 (6H, d, J = 7
Hz), 1.60 (2H, sextet, J = 7Hz), 3.12-3.16 (2H, m), 3.5
6 (2H, septet, J = 7Hz), 3.90 (3H, s), 5.58 (2H, s), 6.58
(1H, d, J = 8Hz), 7.22 (1H, dd, J = 5,8Hz), 7.55 (1H, dt, J
= 1, 8Hz), 7.94 (2H, s), 8.02 (1H, s), 8.63 (1H, dd, J =
(2) 3-acetyl-1- (6-chloro-3,4-methylenedioxybenzyl) -2-propylindole-6
Carboxylic acid methyl ester mp: 210-212 ° C NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.63 (2H, sexte
t, J = 7Hz), 2.37 (3H, s), 3.04-3.08 (2H, m), 3.92 (3H,
s), 5.40 (2H, s), 5.70 (1H, s), 5.90 (2H, s), 6.92 (1
H, s), 7.95 (1H, s), 7.97 (1H, d, J = 8Hz), 8.04 (1H, d, J =
8Hz)
【０２３４】製造例83 ３−アセチル−１−（２−クロロベンジル）−２−エチ
ルインドール−６−カルボン酸メチルエステル（110m
g）のテトラヒドロフラン（５ml）溶液に、１Ｍボラン
−テトラヒドロフラン溶液（0.6ml）を、０℃で一度に
加えた。混合物を20℃で１時間撹拌し、つぎに、水で反
応を止め、酢酸エチルで抽出した。有機層を食塩水で洗
い、硫酸マグネシウムで乾燥し、減圧下で蒸発した。残
留物をシリカゲルクロマトグラフィーに付し、ヘキサン
−酢酸エチル（２：１）混合物で溶出して、１−（２−
クロロベンジル）−２,３−ジエチルインドール−６−
カルボン酸メチルエステル（42mg）を無色結晶として得
た。 mp : 86−88℃ IR (KBr) : 1710, 1240 cm-1 NMR (CDCl3,δ) : 1.13 (3H,t,J=7Hz), 1.30 (3H,t,J=7
Hz), 2.69 (2H,t,J=7Hz), 2.79 (2H,q,J=7Hz), 3.90 (3
H,s), 5.44 (2H,s), 6.17 (1H,d,J=8Hz), 7.00 (1H,t,J
=8Hz), 7.19 (1H,t,J=8Hz), 7.42 (1H,d,J=7.5Hz),7.60
(1H,d,J=8Hz), 7.80 (1H,d,J=8Hz), 7.88 (1H,s) MASS (m/z) : 356 (M++1)Production Example 83 3-Acetyl-1- (2-chlorobenzyl) -2-ethylindole-6-carboxylic acid methyl ester (110 m
To a solution of g) in tetrahydrofuran (5 ml) was added a 1 M borane-tetrahydrofuran solution (0.6 ml) in one portion at 0 ° C. The mixture was stirred at 20 ° C. for 1 hour, then quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was chromatographed on silica gel eluting with a hexane-ethyl acetate (2: 1) mixture to give 1- (2-
Chlorobenzyl) -2,3-diethylindole-6
Carboxylic acid methyl ester (42 mg) was obtained as colorless crystals. mp: 86-88 ° C IR (KBr): 1710, 1240 cm-1 NMR (CDCl3 , δ): 1.13 (3H, t, J = 7Hz), 1.30 (3H, t, J = 7
Hz), 2.69 (2H, t, J = 7Hz), 2.79 (2H, q, J = 7Hz), 3.90 (3
H, s), 5.44 (2H, s), 6.17 (1H, d, J = 8Hz), 7.00 (1H, t, J
= 8Hz), 7.19 (1H, t, J = 8Hz), 7.42 (1H, d, J = 7.5Hz), 7.60
(1H, d, J = 8Hz), 7.80 (1H, d, J = 8Hz), 7.88 (1H, s) MASS (m / z): 356 (M+ +1)
【０２３５】製造例84 ２−プロピルインドール−６−カルボン酸メチルエステ
ル（350mg）と臭化２−クロロベンジル（364mg）とか
ら、製造例54と同様にして、１−（２−クロロベンジ
ル）−２−プロピルインドール−６−カルボン酸メチル
エステル（400mg）を製造した。 NMR (CDCl3,δ) : 0.99 (3H,t,J=8Hz), 1.74 (2H,sexte
t,J=8Hz), 2.60 (2H,t,J=8Hz), 3.87 (3H,s), 5.43 (2
H,s), 6.16 (1H,d,J=8Hz), 6.43 (1H,s), 7.00 (1H,t,J
=8Hz), 7.18 (1H,t,J=8Hz), 7.43 (1H,d,J=8Hz), 7.60
(1H,d,J=8Hz), 7.80 (1H,d,J=8Hz), 7.90 (1H,s)Production Example 84 1- (2-Chlorobenzyl) -methyl was prepared from 2-propylindole-6-carboxylic acid methyl ester (350 mg) and 2-chlorobenzyl bromide (364 mg) in the same manner as in Production Example 54. 2-Propylindole-6-carboxylic acid methyl ester (400 mg) was prepared. NMR (CDCl3 , δ): 0.99 (3H, t, J = 8Hz), 1.74 (2H, sexte
t, J = 8Hz), 2.60 (2H, t, J = 8Hz), 3.87 (3H, s), 5.43 (2
H, s), 6.16 (1H, d, J = 8Hz), 6.43 (1H, s), 7.00 (1H, t, J
= 8Hz), 7.18 (1H, t, J = 8Hz), 7.43 (1H, d, J = 8Hz), 7.60
(1H, d, J = 8Hz), 7.80 (1H, d, J = 8Hz), 7.90 (1H, s)
【０２３６】製造例85 ジメチルホルムアミド（３ml）とオキシ塩化燐（0.056m
l）とからなる溶液に、撹拌下、２−プロピルインドー
ル−６−カルボン酸メチルエステル(187mg)を加え、混
合物を０℃で20分間撹拌した。生じた混合物をアンモニ
ア水（３ml）中に注ぎ、酢酸エチルで抽出した。合わせ
た有機層を食塩水で洗い、つぎに硫酸ナトリウムで乾燥
し、減圧下で蒸発させた。残留物をシリカゲルクロマト
グラフィーに付して、１−（２−クロロベンジル）−３
−ホルミル−２−プロピルインドール−６−カルボン酸
メチルエステル（153mg）を無色油状物として得た。 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.66 (2H,m),
3.01 (2H,t,J=7Hz),3.90 (3H,s), 5.48 (2H,s), 6.29
(1H,d,J=8Hz), 7.06 (1H,t,J=8Hz),7.24 (1H,t,J=8Hz),
7.47 (1H,d,J=8Hz), 7.91 (1H,s), 8.01 (1H,d,J=8H
z), 8.37 (1H,d,J=8Hz), >10 (1H,s)Production Example 85 Dimethylformamide (3 ml) and phosphorus oxychloride (0.056 m
To the solution consisting of l), under stirring, 2-propylindole-6-carboxylic acid methyl ester (187 mg) was added and the mixture was stirred at 0 ° C. for 20 minutes. The resulting mixture was poured into aqueous ammonia (3 ml) and extracted with ethyl acetate. The combined organic layers were washed with brine, then dried over sodium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography to give 1- (2-chlorobenzyl) -3.
-Formyl-2-propylindole-6-carboxylic acid methyl ester (153 mg) was obtained as a colorless oil. NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.66 (2H, m),
3.01 (2H, t, J = 7Hz), 3.90 (3H, s), 5.48 (2H, s), 6.29
(1H, d, J = 8Hz), 7.06 (1H, t, J = 8Hz), 7.24 (1H, t, J = 8Hz),
7.47 (1H, d, J = 8Hz), 7.91 (1H, s), 8.01 (1H, d, J = 8H
z), 8.37 (1H, d, J = 8Hz),> 10 (1H, s)
【０２３７】製造例86 １−（２−クロロベンジル）−２−プロピルインドール
−６−カルボン酸メチルエステル（380mg）と塩化フェ
ニルアセチル（189mg）とから、製造例１−(5)と同様に
して、１−（２−クロロベンジル）−３−フェニルアセ
チル−２−プロピルインドール−６−カルボン酸メチル
エステル（230mg）を製造した。 NMR (CDCl3,δ) : 0.97 (3H,t,J=8Hz), 1.55-1.67 (2H,
m), 3.02-3.07 (2H,m), 3.91 (3H,s), 4.42 (2H,s), 5.
52 (2H,s), 6.24 (1H,d,J=8Hz),7.05 (1H,t,J=8Hz), 7.
20-7.40 (6H,m), 7.46 (1H,d,J=8Hz), 7.97(1H,s), 7.9
9 (1H,d,J=8Hz), 8.11 (1H,d,J=8Hz)Preparation Example 86 1- (2-chlorobenzyl) -2-propylindole-6-carboxylic acid methyl ester (380 mg) and phenylacetyl chloride (189 mg) were prepared in the same manner as in Preparation Example 1- (5). , 1- (2-chlorobenzyl) -3-phenylacetyl-2-propylindole-6-carboxylic acid methyl ester (230 mg) was prepared. NMR (CDCl3 , δ): 0.97 (3H, t, J = 8Hz), 1.55-1.67 (2H,
m), 3.02-3.07 (2H, m), 3.91 (3H, s), 4.42 (2H, s), 5.
52 (2H, s), 6.24 (1H, d, J = 8Hz), 7.05 (1H, t, J = 8Hz), 7.
20-7.40 (6H, m), 7.46 (1H, d, J = 8Hz), 7.97 (1H, s), 7.9
9 (1H, d, J = 8Hz), 8.11 (1H, d, J = 8Hz)
【０２３８】製造例87 製造例81、製造例82、製造例83、製造例85または製造例
86で得た化合物（Ｉ−１）から、製造例55と同様にし
て、下記（1)〜(21)に記載の化合物を製造した。 (1) １−（２−フルオロベンジル）−３−イソブチリル
−２−プロピルインドール−６−カルボン酸 mp : 212−213℃ IR (KBr) : 1685, 1650 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.55-1.68 (2H,m), 3.09-3.14 (2H,m), 3.52-3.62
(1H,m), 5.50 (2H,s), 6.47 (1H,t,J=7.5Hz), 6.97 (1
H,t,J=7.5Hz), 7.15 (1H,t,J=7.5Hz), 7.24-7.30 (1H,
m), 7.95-8.04 (2H,m), 8.08 (1H,s) MASS (m/z) : 380 (M+-1) (2) １−（２−ブロモベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボン酸 mp : 193−194℃ IR (KBr) : 1690, 1670 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 1.57-1.65 (2H,m), 3.01-3.07 (2H,m), 3.52-3.61
(1H,m), 5.49 (2H,s), 6.22 (1H,t,J=7.5Hz), 7.07-7.
18 (2H,m), 7.66 (1H,t,J=7.5Hz), 7.97-8.01 (3H,m) MASS (m/z) : 442 (M+), 440 (M+-2)Production Example 87 Production Example 81, Production Example 82, Production Example 83, Production Example 85, or Production Example
From compound (I-1) obtained in 86, the following compounds (1) to (21) were produced in the same manner as in Production Example 55. (1) 1- (2-fluorobenzyl) -3-isobutyryl-2-propylindole-6-carboxylic acid mp: 212-213 ° C IR (KBr): 1685, 1650 cm−1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.55-1.68 (2H, m), 3.09-3.14 (2H, m), 3.52-3.62
(1H, m), 5.50 (2H, s), 6.47 (1H, t, J = 7.5Hz), 6.97 (1
H, t, J = 7.5Hz), 7.15 (1H, t, J = 7.5Hz), 7.24-7.30 (1H,
m), 7.95-8.04 (2H, m), 8.08 (1H, s) MASS (m / z): 380 (M+ -1) (2) 1- (2-bromobenzyl) -3-isobutyryl-
2-propylindole-6-carboxylic acid mp: 193-194 ° C IR (KBr): 1690, 1670 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.31 (6H, d , J = 7
Hz), 1.57-1.65 (2H, m), 3.01-3.07 (2H, m), 3.52-3.61
(1H, m), 5.49 (2H, s), 6.22 (1H, t, J = 7.5Hz), 7.07-7.
18 (2H, m), 7.66 (1H, t, J = 7.5Hz), 7.97-8.01 (3H, m) MASS (m / z): 442 (M+ ), 440 (M+ -2)
【０２３９】(3) １−（２−ヨードベンジル）−３−イ
ソブチリル−２−プロピルインドール−６−カルボン酸 mp : 210℃ IR (KBr) : 1710, 1640, 1435, 1200 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 1.55-1.68 (2H,m), 3.00-3.06 (2H,m), 3.53-3.62
(1H,m), 5.38 (2H,s), 6.18 (1H,d,J=7.5Hz), 6.99 (1
H,t,J=7.5Hz), 7.14 (1H,t,J=7.5Hz), 7.94 (1H,d,J=7.
5Hz), 7.97-8.03 (3H,m) MASS (m/z) : 488 (M+-1), 61 (bp) (4) ３−イソブチリル−１−（２−メチルベンジル）−
２−プロピルインドール−６−カルボン酸 mp : 186−188℃ IR (KBr) : 1690 cm-1 NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 1.56-1.69 (2H,m), 2.50 (3H,s), 3.02-3.09 (2H,
m), 3.52-3.67 (1H,m), 5.39 (2H,s),6.17 (1H,d,J=7.5
Hz), 6.98 (1H,t,J=7.5Hz), 7.17 (1H,t,J=7.5Hz),7.25
(1H,d,J=7.5Hz), 7.97 (1H,s), 8.00 (2H,s) MASS (m/z) : 378 (M++1), 76 (bp)(3) 1- (2-iodobenzyl) -3-isobutyryl-2-propylindole-6-carboxylic acid mp: 210 ° C. IR (KBr): 1710, 1640, 1435, 1200 cm−1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.31 (6H, d, J = 7
Hz), 1.55-1.68 (2H, m), 3.00-3.06 (2H, m), 3.53-3.62
(1H, m), 5.38 (2H, s), 6.18 (1H, d, J = 7.5Hz), 6.99 (1
H, t, J = 7.5Hz), 7.14 (1H, t, J = 7.5Hz), 7.94 (1H, d, J = 7.
5Hz), 7.97-8.03 (3H, m) MASS (m / z): 488 (M+ -1), 61 (bp) (4) 3-isobutyryl-1- (2-methylbenzyl)-
2-propylindole-6-carboxylic acid mp: 186-188 ° C IR (KBr): 1690 cm-1 NMR (CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.31 (6H, d, J = 7
Hz), 1.56-1.69 (2H, m), 2.50 (3H, s), 3.02-3.09 (2H,
m), 3.52-3.67 (1H, m), 5.39 (2H, s), 6.17 (1H, d, J = 7.5
Hz), 6.98 (1H, t, J = 7.5Hz), 7.17 (1H, t, J = 7.5Hz), 7.25
(1H, d, J = 7.5Hz), 7.97 (1H, s), 8.00 (2H, s) MASS (m / z): 378 (M+ +1), 76 (bp)
【０２４０】(5) ３−イソブチリル−１−（２−メトキ
シベンジル）−２−プロピルインドール−６−カルボン
酸 mp : 190−191℃ IR (KBr) : 1685, 1650, 1250 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.58-1.68 (2H,m), 3.07-3.13 (2H,m), 3.54-3.63
(1H,m), 3.98 (3H,s), 5.45 (2H,s),6.30 (1H,d,J=7.5
Hz), 6.75 (1H,t,J=7.5Hz), 6.94 (1H,d,J=7.5Hz),7.24
(1H,t,J=7.5Hz), 7.94-8.02 (2H,m), 8.05 (1H,s) MASS (m/z) : 394 (M++1), 76 (bp) (6) １−（２−シアノベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボン酸 mp : 213.5−215℃ IR (KBr) : 2220, 1717 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 1.53-1.67 (2H,m), 3.04-3.09 (2H,m), 3.52-3.62
(1H,m), 5.69 (2H,s), 6.47-6.50(1H,m), 7.39-7.44
(2H,m), 7.77-7.80 (1H,m), 7.99-8.04 (3H,m) MASS (m/z) : 389 (M+-1), 76 (bp)(5) 3-isobutyryl-1- (2-methoxybenzyl) -2-propylindole-6-carboxylic acid mp: 190-191 ° C IR (KBr): 1685, 1650, 1250 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.58-1.68 (2H, m), 3.07-3.13 (2H, m), 3.54-3.63
(1H, m), 3.98 (3H, s), 5.45 (2H, s), 6.30 (1H, d, J = 7.5
Hz), 6.75 (1H, t, J = 7.5Hz), 6.94 (1H, d, J = 7.5Hz), 7.24
(1H, t, J = 7.5Hz), 7.94-8.02 (2H, m), 8.05 (1H, s) MASS (m / z): 394 (M+ +1), 76 (bp) (6) 1- (2-cyanobenzyl) -3-isobutyryl-
2-propylindole-6-carboxylic acid mp: 213.5-215 ° C IR (KBr): 2220, 1717 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.31 (6H, d , J = 7
Hz), 1.53-1.67 (2H, m), 3.04-3.09 (2H, m), 3.52-3.62
(1H, m), 5.69 (2H, s), 6.47-6.50 (1H, m), 7.39-7.44
(2H, m), 7.77-7.80 (1H, m), 7.99-8.04 (3H, m) MASS (m / z): 389 (M+ -1), 76 (bp)
【０２４１】(7) ３−イソブチリル−１−（２−ニトロ
ベンジル）−２−プロピルインドール−６−カルボン酸 mp : 214−215℃ IR (KBr) : 1695, 1655, 1545 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.32 (6H,d,J=7
Hz), 1.57-1.65 (2H,m), 3.03 (2H,t,J=7Hz), 3.54-3.6
3 (1H,m), 5.89 (2H,s), 6.28 (1H,d,J=7.5Hz), 7.39-
7.51 (2H,m), 7.92 (1H,s), 8.02 (2H,s), 8.30 (1H,d,
J=7.5Hz) MASS (m/z) : 409 (M++1) (8) １−（２,６−ジクロロベンジル）−３−イソブチ
リル−２−プロピルインドール−６−カルボン酸 mp : 241.5−243℃ (分解) IR (KBr) : 1675, 1650 cm-1 NMR (CDCl3,δ) : 0.99 (3H,t,J=7Hz), 1.28 (6H,d,J=7
Hz), 1.39-1.52 (2H,m), 3.17-3.22 (2H,m), 3.50-3.59
(1H,m), 5.71 (2H,s), 7.24-7.28(1H,m), 7.37-7.40
(2H,m), 7.94 (2H,q,J=7.5Hz), 8.10 (1H,s) MASS (m/z) : 432 (M++1), 76 (bp)(7) 3-isobutyryl-1- (2-nitrobenzyl) -2-propylindole-6-carboxylic acid mp: 214-215 ° C IR (KBr): 1695, 1655, 1545 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.32 (6H, d, J = 7
Hz), 1.57-1.65 (2H, m), 3.03 (2H, t, J = 7Hz), 3.54-3.6
3 (1H, m), 5.89 (2H, s), 6.28 (1H, d, J = 7.5Hz), 7.39-
7.51 (2H, m), 7.92 (1H, s), 8.02 (2H, s), 8.30 (1H, d,
J = 7.5Hz) MASS (m / z): 409 (M++ 1) (8) 1- (2,6-dichlorobenzyl) -3-isobutyryl-2-propylindole-6-carboxylic acid mp: 241.5- 243 ° C (decomposition) IR (KBr): 1675, 1650 cm-1 NMR (CDCl3 , δ): 0.99 (3H, t, J = 7Hz), 1.28 (6H, d, J = 7
Hz), 1.39-1.52 (2H, m), 3.17-3.22 (2H, m), 3.50-3.59
(1H, m), 5.71 (2H, s), 7.24-7.28 (1H, m), 7.37-7.40
(2H, m), 7.94 (2H, q, J = 7.5Hz), 8.10 (1H, s) MASS (m / z): 432 (M+ +1), 76 (bp)
【０２４２】(9) １−（２−クロロ−４−フルオロベン
ジル）−３−イソブチリル−２−プロピルインドール−
６−カルボン酸 mp : 243−244℃ IR (KBr) : 1676, 1648, 1491 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.60 (2H,sextet,J=7Hz), 3.01-3.07 (2H,m), 3.5
3-3.62 (1H,m), 5.49 (2H,s),6.20-6.26 (1H,m), 6.79
(1H,ddd,J=7.5, 7.5, 1Hz), 7.23 (1H,dd,J=7.5, 1Hz),
7.96 (1H,s), 7.99 (1H,d,J=7.5Hz) MASS (m/z) : 414 (M+-1) (10) １−（４−ブロモ−２−フルオロベンジル）−３
−イソブチリル−２−プロピルインドール−６−カルボ
ン酸 mp : 210−211℃ IR (KBr) : 1677, 1646, 1486 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.55-1.67 (2H,m), 3.07-3.12 (2H,m), 3.52-3.60
(1H,m), 5.46 (2H,s), 6.32 (1H,t,J=7.5Hz), 7.11 (1
H,d,J=7.5Hz), 7.35 (1H,d,J=7.5Hz), 7.96-8.03(3H,m) MASS (m/z) : 460 (M+), 458 (M+-2)(9) 1- (2-chloro-4-fluorobenzyl) -3-isobutyryl-2-propylindole-
6-carboxylic acid mp: 243-244 ° C IR (KBr): 1676, 1648, 1491 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.60 (2H, sextet, J = 7Hz), 3.01-3.07 (2H, m), 3.5
3-3.62 (1H, m), 5.49 (2H, s), 6.20-6.26 (1H, m), 6.79
(1H, ddd, J = 7.5, 7.5, 1Hz), 7.23 (1H, dd, J = 7.5, 1Hz),
7.96 (1H, s), 7.99 (1H, d, J = 7.5Hz) MASS (m / z): 414 (M+ -1) (10) 1- (4-bromo-2-fluorobenzyl) -3
-Isobutyryl-2-propylindole-6-carboxylic acid mp: 210-211 ° C IR (KBr): 1677, 1646, 1486 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.55-1.67 (2H, m), 3.07-3.12 (2H, m), 3.52-3.60
(1H, m), 5.46 (2H, s), 6.32 (1H, t, J = 7.5Hz), 7.11 (1
H, d, J = 7.5Hz), 7.35 (1H, d, J = 7.5Hz), 7.96-8.03 (3H, m) MASS (m / z): 460 (M+ ), 458 (M+ -2)
【０２４３】(11) ３−ベンゾイル−１−（２−クロロ
ベンジル）−２−プロピルインドール−６−カルボン酸 NMR (DMSO-d6,δ) : 0.95 (3H,t,J=8Hz), 1.66 (2H,sex
tet,J=8Hz), 2.98(2H,t,J=8Hz), 5.55 (2H,s), 6.35 (1
H,dd,J=1, 8Hz), 7.09 (1H,dt,J=1, 8Hz), 7.20-7.27
(2H,m), 7.48 (1H,t,J=8Hz), 7.57-7.62 (1H,m),7.72-
7.82 (3H,m), 7.98 (1H,s) (12) １−（２−クロロベンジル）−３−シアノ−２−
プロピルインドール−６−カルボン酸 mp : 239.5−241℃ IR (KBr) : 2224, 1671, 1287, 1264 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.70 (2H,sexte
t,J=7Hz), 2.89 (2H,t,J=7Hz), 5.50 (2H,s), 6.25 (1
H,d,J=7.5Hz), 7.18 (1H,ddt,J=7.5,7.5, 1Hz), 7.25
(1H,ddd,J=7.5, 7.5, 1Hz), 7.47 (1H,d,J=7.5Hz),7.78
(1H,dd,J=7.5, 1Hz), 7.99 (1H,d,J=1Hz), 8.01 (1H,
d,J=7.5Hz) MASS (m/z) : 351 (M+-1)(11) 3-benzoyl-1- (2-chlorobenzyl) -2-propylindole-6-carboxylic acid NMR (DMSO-d6 , δ): 0.95 (3H, t, J = 8 Hz), 1.66 (2H, sex
tet, J = 8Hz), 2.98 (2H, t, J = 8Hz), 5.55 (2H, s), 6.35 (1
H, dd, J = 1,8Hz), 7.09 (1H, dt, J = 1,8Hz), 7.20-7.27
(2H, m), 7.48 (1H, t, J = 8Hz), 7.57-7.62 (1H, m), 7.72-
7.82 (3H, m), 7.98 (1H, s) (12) 1- (2-chlorobenzyl) -3-cyano-2-
Propylindole-6-carboxylic acid mp: 239.5-241 ° C IR (KBr): 2224, 1671, 1287, 1264 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.70 (2H , sexte
t, J = 7Hz), 2.89 (2H, t, J = 7Hz), 5.50 (2H, s), 6.25 (1
(H, d, J = 7.5Hz), 7.18 (1H, ddt, J = 7.5,7.5, 1Hz), 7.25
(1H, ddd, J = 7.5,7.5,1Hz), 7.47 (1H, d, J = 7.5Hz), 7.78
(1H, dd, J = 7.5, 1Hz), 7.99 (1H, d, J = 1Hz), 8.01 (1H,
d, J = 7.5Hz) MASS (m / z): 351 (M+ -1)
【０２４４】(13) １−（２−クロロベンジル）−２−
エチル−３−イソブチリルインドール−６−カルボン酸 NMR (CDCl3,δ) : 1.22 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 3.12 (2H,q,J=7Hz), 3.57 (1H,m), 5.51 (2H,s),
6.23 (1H,d,J=8Hz), 7.04 (1H,t,J=8Hz), 7.22 (1H,t,J
=8Hz), 7.47 (1H,d,J=8Hz), 7.95-8.05 (3H,m) (14) １−（２−クロロベンジル）−３−イソブチリル
−２−メチルインドール−６−カルボン酸 NMR (CDCl3,δ) : 1.31 (6H,d,J=7Hz), 2.72 (3H,s),
3.56 (1H,m), 5.51(2H,s), 6.25 (1H,d,J=8Hz), 7.05
(1H,t,J=8Hz), 7.23 (1H,t,J=8Hz),7.46 (1H,d,J=8Hz),
8.05 (3H,s)(13) 1- (2-chlorobenzyl) -2-
Ethyl-3-isobutyrylindole-6-carboxylic acid NMR (CDCl3 , δ): 1.22 (3H, t, J = 7 Hz), 1.31 (6H, d, J = 7
Hz), 3.12 (2H, q, J = 7Hz), 3.57 (1H, m), 5.51 (2H, s),
6.23 (1H, d, J = 8Hz), 7.04 (1H, t, J = 8Hz), 7.22 (1H, t, J
= 8Hz), 7.47 (1H, d, J = 8Hz), 7.95-8.05 (3H, m) (14) 1- (2-chlorobenzyl) -3-isobutyryl-2-methylindole-6-carboxylic acid NMR ( CDCl3 , δ): 1.31 (6H, d, J = 7Hz), 2.72 (3H, s),
3.56 (1H, m), 5.51 (2H, s), 6.25 (1H, d, J = 8Hz), 7.05
(1H, t, J = 8Hz), 7.23 (1H, t, J = 8Hz), 7.46 (1H, d, J = 8Hz),
8.05 (3H, s)
【０２４５】(15) １−（２−クロロベンジル）−３−
イソブチリル−２−メトキシメチルインドール−６−カ
ルボン酸 NMR (CDCl3,δ) : 1.32 (6H,d,J=7Hz), 3.35 (3H,s),
3.58 (1H,m), 4.94(2H,s), 5.68 (2H,s), 6.28 (1H,d,J
=8Hz), 7.03 (1H,t,J=8Hz), 7.20(1H,t,J=8Hz), 7.45
(1H,d,J=8Hz), 8.0-8.05 (3H,m) (16) １−（２−クロロベンジル）−３−イソブチリル
インドール−６−カルボン酸 NMR (CDCl3,δ) : 1.25 (6H,d,J=7Hz), 3.30 (1H,m),
5.52 (2H,s), 6.79(1H,d,J=8Hz), 7.18 (1H,t,J=8Hz),
7.28 (1H,t,J=8Hz), 7.47 (1H,d,J=8Hz), 7.91 (1H,s),
8.03 (1H,d,J=8Hz), 8.12 (1H,s), 8.48 (1H,d,J=8Hz)(15) 1- (2-chlorobenzyl) -3-
Isobutyryl-2-methoxymethyl-indole-6-carboxylic acidNMR (CDCl 3, δ): 1.32 (6H, d, J = 7Hz), 3.35 (3H, s),
3.58 (1H, m), 4.94 (2H, s), 5.68 (2H, s), 6.28 (1H, d, J
= 8Hz), 7.03 (1H, t, J = 8Hz), 7.20 (1H, t, J = 8Hz), 7.45
(1H, d, J = 8 Hz), 8.0-8.05 (3H, m) (16) 1- (2-chlorobenzyl) -3-isobutyrylindole-6-carboxylic acid NMR (CDCl3 , δ): 1.25 (6H, d, J = 7Hz), 3.30 (1H, m),
5.52 (2H, s), 6.79 (1H, d, J = 8Hz), 7.18 (1H, t, J = 8Hz),
7.28 (1H, t, J = 8Hz), 7.47 (1H, d, J = 8Hz), 7.91 (1H, s),
8.03 (1H, d, J = 8Hz), 8.12 (1H, s), 8.48 (1H, d, J = 8Hz)
【０２４６】(17) ３−イソブチリル−２−プロピル−
１−（２−ピリジルメチル）インドール−６−カルボン
酸 NMR (DMSO-d6,δ) : 0.92 (3H,t,J=7Hz), 1.16 (6H,d,J
=7Hz), 1.46 (2H,sextet,J=7Hz), 3.12-3.17 (2H,m),
3.52 (2H,septet,J=7Hz), 5.72(2H,s), 7.16 (1H,d,J=8
Hz), 7.29 (1H,dd,J=5, 8Hz), 7.76 (1H,t,J=8Hz), 7.8
1 (1H,d,J=8Hz), 7.96 (1H,t,J=8Hz), 8.06 (1H,s), 8.
48(1H,d,J=5Hz) (18) １−（２−クロロベンジル）−２,３−ジエチルイ
ンドール−６−カルボン酸 mp : 258−259℃ (分解) IR (KBr) : 1675, 1290 cm-1 NMR (CDCl3,δ) : 1.14 (3H,t,J=7Hz), 1.30 (3H,t,J=7
Hz), 2.71 (2H,q,J=7Hz), 2.80 (2H,q,J=7Hz), 5.45 (2
H,s), 6.18 (1H,d,J=7.5Hz), 7.00(1H,t,J=7.5Hz), 7.1
9 (1H,t,J=7.5Hz), 7.42 (1H,d,J=7.5Hz), 7.62(1H,d,J
=7.5Hz), 7.84 (1H,d,J=7.5Hz), 7.91 (1H,s) MASS (m/z) : 340 (M+-1)(17) 3-isobutyryl-2-propyl-
1- (2-pyridylmethyl) indole-6-carboxylic acid NMR (DMSO-d6 , δ): 0.92 (3H, t, J = 7 Hz), 1.16 (6H, d, J
= 7Hz), 1.46 (2H, sextet, J = 7Hz), 3.12-3.17 (2H, m),
3.52 (2H, septet, J = 7Hz), 5.72 (2H, s), 7.16 (1H, d, J = 8
Hz), 7.29 (1H, dd, J = 5,8Hz), 7.76 (1H, t, J = 8Hz), 7.8
1 (1H, d, J = 8Hz), 7.96 (1H, t, J = 8Hz), 8.06 (1H, s), 8.
48 (1H, d, J = 5 Hz) (18) 1- (2-chlorobenzyl) -2,3-diethylindole-6-carboxylic acid mp: 258-259 ° C. (decomposition) IR (KBr): 1675, 1290 cm-1 NMR (CDCl3 , δ): 1.14 (3H, t, J = 7Hz), 1.30 (3H, t, J = 7
Hz), 2.71 (2H, q, J = 7Hz), 2.80 (2H, q, J = 7Hz), 5.45 (2
H, s), 6.18 (1H, d, J = 7.5Hz), 7.00 (1H, t, J = 7.5Hz), 7.1
9 (1H, t, J = 7.5Hz), 7.42 (1H, d, J = 7.5Hz), 7.62 (1H, d, J
= 7.5Hz), 7.84 (1H, d, J = 7.5Hz), 7.91 (1H, s) MASS (m / z): 340 (M+ -1)
【０２４７】(19) １−（２−クロロベンジル）−３−
ホルミル−２−プロピルインドール−６−カルボン酸 NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.67 (2H,m),
3.03 (2H,t,J=7Hz),5.50 (2H,s), 6.40 (1H,d,J=8Hz),
7.08 (1H,t,J=8Hz), 7.24 (1H,t,J=8Hz), 7.48 (1H,d,J
=8Hz), 7.98 (1H,s), 8.07 (1H,d,J=8Hz), 8.40(1H,d,J
=8Hz) (20) （２−クロロベンジル）−３−フェニルアセチル
−２−プロピルインドール−６−カルボン酸 NMR (DMSO-d6,δ) : 0.90 (3H,t,J=8Hz), 1.45 (2H,sex
et,J=8Hz), 3.04-3.08(2H,m), 4.43 (2H,s), 5.68 (2H,
s), 6.27 (1H,d,J=8Hz), 7.18 (1H,t,J=8Hz), 7.23-7.3
5 (6H,m), 7.58 (1H,d,J=8Hz), 7.85 (1H,d,J=8Hz),7.9
8 (1H,s), 8.19 (1H,d,J=8Hz)(19) 1- (2-chlorobenzyl) -3-
Formyl-2-propyl indole-6-carboxylic acidNMR (CDCl 3, δ): 1.01 (3H, t, J = 7Hz), 1.67 (2H, m),
3.03 (2H, t, J = 7Hz), 5.50 (2H, s), 6.40 (1H, d, J = 8Hz),
7.08 (1H, t, J = 8Hz), 7.24 (1H, t, J = 8Hz), 7.48 (1H, d, J
= 8Hz), 7.98 (1H, s), 8.07 (1H, d, J = 8Hz), 8.40 (1H, d, J
(8) (20) (2-chlorobenzyl) -3-phenylacetyl-2-propylindole-6-carboxylic acid NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 8Hz), 1.45 ( 2H, sex
et, J = 8Hz), 3.04-3.08 (2H, m), 4.43 (2H, s), 5.68 (2H,
s), 6.27 (1H, d, J = 8Hz), 7.18 (1H, t, J = 8Hz), 7.23-7.3
5 (6H, m), 7.58 (1H, d, J = 8Hz), 7.85 (1H, d, J = 8Hz), 7.9
8 (1H, s), 8.19 (1H, d, J = 8Hz)
【０２４８】(21) ３−アセチル−１−（６−クロロ−
３,４−メチレンジオキシベンジル）−２−プロピルイ
ンドール−６−カルボン酸 mp : 238−239℃ NMR (CDCl3-CD3OD=1:1,δ) : 1.06 (3H,t,J=8Hz), 1.65
(2H,sextet,J=8Hz),2.76 (3H,s), 3.08-3.14 (2H,m),
5.48 (2H,s), 5.74 (1H,s), 5.92 (2H,s), 6.96 (1H,
s), 7.99 (1H,d,J=8Hz), 8.02 (1H,s), 8.08 (1H,d,J=8
Hz)(21) 3-acetyl-1- (6-chloro-
3,4-methylenedioxybenzyl) -2-propylindole-6-carboxylic acid mp: 238-239 ° C NMR (CDCl3 -CD3 OD = 1: 1, δ): 1.06 (3H, t, J = 8Hz) ), 1.65
(2H, sextet, J = 8Hz), 2.76 (3H, s), 3.08-3.14 (2H, m),
5.48 (2H, s), 5.74 (1H, s), 5.92 (2H, s), 6.96 (1H,
s), 7.99 (1H, d, J = 8Hz), 8.02 (1H, s), 8.08 (1H, d, J = 8
Hz)
【０２４９】製造例88 ３−アセチル−２−エチルインドール−６−カルボン酸
メチルエステル（100mg）と臭化２−クロロベンジル
（0.06ml）とから、製造例54と同様にして、３−アセチ
ル−１−（２−クロロベンジル）−２−エチルインドー
ル−６−カルボン酸メチルエステル（170mg）を製造し
た。この生成物は、精製することなく、直接、下記製造
例89で使用した。Production Example 88 3-Acetyl-2-ethylindole-6-carboxylic acid methyl ester (100 mg) and 2-chlorobenzyl bromide (0.06 ml) were prepared in the same manner as in Production Example 54 to give 3-acetyl- 1- (2-Chlorobenzyl) -2-ethylindole-6-carboxylic acid methyl ester (170 mg) was prepared. This product was used directly in Purification Example 89 below without purification.
【０２５０】製造例89 ３−アセチル−１−（２−クロロベンジル）−２−エチ
ルインドール−６−カルボン酸メチルエステル（170m
g）から、製造例55と同様にして、３−アセチル−１−
（２−クロロベンジル）−２−エチルインドール−６−
カルボン酸（137mg）を製造した。 NMR (DMSO-d6,δ) : 1.11 (3H,t,J=7Hz), 2.67 (3H,s),
3.11 (2H,q,J=7Hz),5.68 (2H,s), 6.26 (1H,d,J=8Hz),
7.19 (1H,t,J=8Hz), 7.32 (1H,t,J=8Hz), 7.58 (1H,d,
J=8Hz), 7.83 (1H,d,J=8Hz), 7.94 (1H,s), 8.13(1H,d,
J=8Hz)Production Example 89 Methyl 3-acetyl-1- (2-chlorobenzyl) -2-ethylindole-6-carboxylate (170m
From g), as in Production Example 55, 3-acetyl-1-
(2-chlorobenzyl) -2-ethylindole-6
Carboxylic acid (137 mg) was prepared. NMR (DMSO-d6 , δ): 1.11 (3H, t, J = 7Hz), 2.67 (3H, s),
3.11 (2H, q, J = 7Hz), 5.68 (2H, s), 6.26 (1H, d, J = 8Hz),
7.19 (1H, t, J = 8Hz), 7.32 (1H, t, J = 8Hz), 7.58 (1H, d,
J = 8Hz), 7.83 (1H, d, J = 8Hz), 7.94 (1H, s), 8.13 (1H, d,
(J = 8Hz)
【０２５１】製造例90 製造例87および製造例88で得た化合物（Ｉ−２）から、
製造例56と同様にして、下記(1)〜(19)に記載の化合物
を製造した。 (1) １−（２−フルオロベンジル）−３−イソブチリル
−２−プロピルインドール−６−カルボキサミド mp : 198℃ IR (KBr) : 3200, 1650, 1610 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.55-1.64 (2H,m), 3.06-3.12 (2H,m), 3.50-3.60
(1H,m), 5.50 (2H,s), 6.42 (1H,t,J=7.5Hz), 6.95 (2
H,t,J=7.5Hz), 7.09-7.17 (1H,m), 7.22-7.28 (1H,m),
7.61 (1H,t,J=7.5Hz), 7.90 (1H,s), 7.96 (1H,t,J=7.5
Hz) MASS (m/z) : 381 (M++1) (2) １−（２−ブロモベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボキサミド mp : 173−174℃ IR (KBr) : 3400, 1660, 1630 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.57-1.68 (2H,m), 3.00-3.06 (2H,m), 3.51-3.61
(1H,m), 5.46 (2H,s), 6.20 (1H,t,J=7.5Hz), 7.05-7.
18 (2H,m), 7.60-7.66 (1H,m), 7.83 (1H,s), 7.99(1H,
t,J=7.5Hz) MASS (m/z) : 443 (M++2), 441 (M+), 76 (bp)Preparation Example 90 From the compound (I-2) obtained in Preparation Example 87 and Preparation Example 88,
The following compounds (1) to (19) were produced in the same manner as in Production Example 56. (1) 1- (2-Fluorobenzyl) -3-isobutyryl-2-propylindole-6-carboxamide mp: 198 ° C IR (KBr): 3200, 1650, 1610 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.55-1.64 (2H, m), 3.06-3.12 (2H, m), 3.50-3.60
(1H, m), 5.50 (2H, s), 6.42 (1H, t, J = 7.5Hz), 6.95 (2
(H, t, J = 7.5Hz), 7.09-7.17 (1H, m), 7.22-7.28 (1H, m),
7.61 (1H, t, J = 7.5Hz), 7.90 (1H, s), 7.96 (1H, t, J = 7.5Hz)
Hz) MASS (m / z): 381 (M+ +1) (2) 1- (2-bromobenzyl) -3-isobutyryl-
2-propylindole-6-carboxamide mp: 173-174 ° C IR (KBr): 3400, 1660, 1630 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.57-1.68 (2H, m), 3.00-3.06 (2H, m), 3.51-3.61
(1H, m), 5.46 (2H, s), 6.20 (1H, t, J = 7.5Hz), 7.05-7.
18 (2H, m), 7.60-7.66 (1H, m), 7.83 (1H, s), 7.99 (1H,
t, J = 7.5Hz) MASS (m / z): 443 (M+ +2), 441 (M+ ), 76 (bp)
【０２５２】(3) １−（２−ヨードベンジル）−３−イ
ソブチリル−２−プロピルインドール−６−カルボキサ
ミド mp : 186−187℃ IR (KBr) : 3400, 1665, 1640 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.54-1.67 (2H,m), 2.99-3.05 (2H,m), 3.51-3.60
(1H,m), 5.39 (2H,s), 6.15 (1H,d,J=7.5Hz), 6.99 (1
H,t,J=7.5Hz), 7.11 (1H,t,J=7.5Hz), 7.64 (1H,d,J=7.
5Hz), 7.82 (1H,s), 7.92 (1H,d,J=7Hz), 7.99 (1H,d,J
=7Hz) MASS (m/z) : 489 (M++1), 76 (bp) (4) ３−イソブチリル−１−（２−メチルベンジル）−
２−プロピルインドール−６−カルボキサミド mp : 190−191℃ IR (KBr) : 3395, 1650, 1625, 1410 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 1.54-1.68 (2H,m), 2.49 (3H,s), 3.00-3.07 (2H,
m), 3.52-3.61 (1H,m), 5.38 (2H,s),6.14 (1H,d,J=7.5
Hz), 6.98 (1H,t,J=7.5Hz), 7.17 (1H,t,J=7.5Hz),7.24
(1H,d,J=7.5Hz), 7.60 (1H,d,J=7.5Hz), 7.82 (1H,s),
7.99 (1H,d,J=7.5Hz) MASS (m/z) : 377 (M++1), 76 (bp)(3) 1- (2-Iodobenzyl) -3-isobutyryl-2-propylindole-6-carboxamide mp: 186-187 ° C IR (KBr): 3400, 1665, 1640 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.54-1.67 (2H, m), 2.99-3.05 (2H, m), 3.51-3.60
(1H, m), 5.39 (2H, s), 6.15 (1H, d, J = 7.5Hz), 6.99 (1
H, t, J = 7.5Hz), 7.11 (1H, t, J = 7.5Hz), 7.64 (1H, d, J = 7.
5Hz), 7.82 (1H, s), 7.92 (1H, d, J = 7Hz), 7.99 (1H, d, J
= 7Hz) MASS (m / z): 489 (M+ +1), 76 (bp) (4) 3-isobutyryl-1- (2-methylbenzyl)-
2-propylindole-6-carboxamide mp: 190-191 ° C IR (KBr): 3395, 1650, 1625, 1410 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.31 ( 6H, d, J = 7
Hz), 1.54-1.68 (2H, m), 2.49 (3H, s), 3.00-3.07 (2H,
m), 3.52-3.61 (1H, m), 5.38 (2H, s), 6.14 (1H, d, J = 7.5
Hz), 6.98 (1H, t, J = 7.5Hz), 7.17 (1H, t, J = 7.5Hz), 7.24
(1H, d, J = 7.5Hz), 7.60 (1H, d, J = 7.5Hz), 7.82 (1H, s),
7.99 (1H, d, J = 7.5Hz) MASS (m / z): 377 (M+ +1), 76 (bp)
【０２５３】(5) ３−イソブチリル−１−（２−メトキ
シベンジル）−２−プロピルインドール−６−カルボキ
サミド mp : 174−175℃ IR (KBr) : 3370, 1655, 1650, 1625 cm-1 NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.57-1.69 (2H,m), 3.05-3.10 (2H,m), 3.52-3.61
(1H,m), 3.97 (3H,s), 5.43 (2H,s),6.24 (1H,d,J=7.5
Hz), 6.74 (2H,t,J=7.5Hz), 6.93 (1H,d,J=7.5Hz),7.24
(1H,t,J=7.5Hz), 7.59 (1H,d,J=7.5Hz), 7.88 (1H,s),
7.97 (1H,d,J=7.5Hz) MASS (m/z) : 393 (M++1), 76 (bp) (6) １−（２−シアノベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボキサミド mp : 143−144℃ IR (KBr) : 3377, 3190, 2227, 1645 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.52-1.65 (2H,m), 3.02-3.08 (2H,m), 3.50-3.59
(1H,m), 5.68 (2H,s), 6.45-6.49(1H,m), 7.38-7.43
(2H,m), 7.65 (1H,d,J=7.5Hz), 7.74-7.78 (1H,m),7.87
(1H,s), 7.99 (1H,d,J=7.5Hz) MASS (m/z) : 388 (M++1), 62 (bp)(5) 3-isobutyryl-1- (2-methoxybenzyl) -2-propylindole-6-carboxamide mp: 174-175 ° C IR (KBr): 3370, 1655, 1650, 1625 cm-1 NMR ( CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.57-1.69 (2H, m), 3.05-3.10 (2H, m), 3.52-3.61
(1H, m), 3.97 (3H, s), 5.43 (2H, s), 6.24 (1H, d, J = 7.5
Hz), 6.74 (2H, t, J = 7.5Hz), 6.93 (1H, d, J = 7.5Hz), 7.24
(1H, t, J = 7.5Hz), 7.59 (1H, d, J = 7.5Hz), 7.88 (1H, s),
7.97 (1H, d, J = 7.5Hz) MASS (m / z): 393 (M+ +1), 76 (bp) (6) 1- (2-cyanobenzyl) -3-isobutyryl-
2-propylindole-6-carboxamide mp: 143-144 ° C IR (KBr): 3377, 3190, 2227, 1645 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.30 ( 6H, d, J = 7
Hz), 1.52-1.65 (2H, m), 3.02-3.08 (2H, m), 3.50-3.59
(1H, m), 5.68 (2H, s), 6.45-6.49 (1H, m), 7.38-7.43
(2H, m), 7.65 (1H, d, J = 7.5Hz), 7.74-7.78 (1H, m), 7.87
(1H, s), 7.99 (1H, d, J = 7.5Hz) MASS (m / z): 388 (M+ +1), 62 (bp)
【０２５４】(7) ３−イソブチリル−１−（２−ニトロ
ベンジル）−２−プロピルインドール−６−カルボキサ
ミド mp : 181−182℃ IR (KBr) : 3190, 1670, 1610, 1535, 1400 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.32 (6H,d,J=7
Hz), 1.58-1.67 (2H,m), 3.02 (2H,t,J=7Hz), 3.52-3.6
1 (1H,m), 5.89 (2H,s), 6.27 (1H,d,J=7.5Hz), 7.39-
7.50 (2H,m), 7.63 (1H,d,J=7.5Hz), 7.80 (1H,s),7.99
(1H,d,J=7.5Hz), 8.28 (1H,d,J=7.5Hz) MASS (m/z) : 408 (M++1), 76 (bp) (8) １−（２,６−ジクロロベンジル）−３−イソブチ
リル−２−プロピルインドール−６−カルボキサミド mp : 207.5−209℃ IR (KBr) : 3395, 1650, 1615 cm-1 NMR (CDCl3,δ) : 0.98 (3H,t,J=7Hz), 1.28 (6H,d,J=7
Hz), 1.39-1.50 (2H,m), 3.16-3.21 (2H,m), 3.49-3.58
(1H,m), 5.70 (2H,s), 7.22-7.25(1H,m), 7.35-7.39
(2H,m), 7.60 (1H,d,J=7.5Hz), 7.86-7.90 (2H,m),7.99
(1H,d,J=7.5Hz) MASS (m/z) : 431 (M++1), 76 (bp)(7) 3-Isobutyryl-1- (2-nitrobenzyl) -2-propylindole-6-carboxamide mp: 181-182 ° C IR (KBr): 3190, 1670, 1610, 1535, 1400 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.32 (6H, d, J = 7
Hz), 1.58-1.67 (2H, m), 3.02 (2H, t, J = 7Hz), 3.52-3.6
1 (1H, m), 5.89 (2H, s), 6.27 (1H, d, J = 7.5Hz), 7.39-
7.50 (2H, m), 7.63 (1H, d, J = 7.5Hz), 7.80 (1H, s), 7.99
(1H, d, J = 7.5Hz), 8.28 (1H, d, J = 7.5Hz) MASS (m / z): 408 (M+ +1), 76 (bp) (8) 1- (2,6 -Dichlorobenzyl) -3-isobutyryl-2-propylindole-6-carboxamide mp: 207.5-209 ° C IR (KBr): 3395, 1650, 1615 cm-1 NMR (CDCl3 , δ): 0.98 (3H, t, J = 7Hz), 1.28 (6H, d, J = 7
Hz), 1.39-1.50 (2H, m), 3.16-3.21 (2H, m), 3.49-3.58
(1H, m), 5.70 (2H, s), 7.22-7.25 (1H, m), 7.35-7.39
(2H, m), 7.60 (1H, d, J = 7.5Hz), 7.86-7.90 (2H, m), 7.99
(1H, d, J = 7.5Hz) MASS (m / z): 431 (M+ +1), 76 (bp)
【０２５５】(9) １−（２−クロロ−４−フルオロベン
ジル）−３−イソブチリル−２−プロピルインドール−
６−カルボキサミド mp : 192−193℃ IR (KBr) : 3336, 3180, 1650, 1494, 1411 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.53-1.65 (2H,m), 3.01-3.07 (2H,m), 3.50-3.60
(1H,m), 5.47 (2H,s), 6.20 (1H,dd,J=8, 7.5Hz), 6.7
8 (1H,ddd,J=7.5, 7.5, 1Hz), 7.23 (1H,dd,J=8,1Hz),
7.63 (1H,d,J=7.5Hz), 7.85 (1H,s), 7.99 (1H,d,J=8H
z) MASS (m/z) : 415 (M++1), 76 (bp) (10) １−（４−ブロモ−２−フルオロベンジル）−３
−イソブチリル−２−プロピルインドール−６−カルボ
キサミド mp : 197−198.5℃ IR (KBr) : 3377, 3189, 1652, 1617, 1487, 1408 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.53-1.64 (2H,m), 3.05-3.11 (2H,m), 3.48-3.60
(1H,m), 5.44 (2H,s), 6.29 (1H,t,J=7.5Hz), 7.09 (1
H,d,J=7.5Hz), 7.33 (1H,dd,J=7.5, 1Hz), 7.62 (1H,d,
J=7.5Hz), 7.90 (1H,d,J=1Hz), 7.97 (1H,d,J=7.5Hz) MASS (m/z) : 461 (M++1), 459 (M+), 76 (bp)(9) 1- (2-chloro-4-fluorobenzyl) -3-isobutyryl-2-propylindole-
6-carboxamide mp: 192-193 ° C IR (KBr): 3336, 3180, 1650, 1494, 1411 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H, d , J = 7
Hz), 1.53-1.65 (2H, m), 3.01-3.07 (2H, m), 3.50-3.60
(1H, m), 5.47 (2H, s), 6.20 (1H, dd, J = 8,7.5Hz), 6.7
8 (1H, dd, J = 7.5, 7.5, 1Hz), 7.23 (1H, dd, J = 8,1Hz),
7.63 (1H, d, J = 7.5Hz), 7.85 (1H, s), 7.99 (1H, d, J = 8H
z) MASS (m / z): 415 (M+ +1), 76 (bp) (10) 1- (4-bromo-2-fluorobenzyl) -3
-Isobutyryl-2-propylindole-6-carboxamide mp: 197-198.5 ° C IR (KBr): 3377, 3189, 1652, 1617, 1487, 1408 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.53-1.64 (2H, m), 3.05-3.11 (2H, m), 3.48-3.60
(1H, m), 5.44 (2H, s), 6.29 (1H, t, J = 7.5Hz), 7.09 (1
H, d, J = 7.5Hz), 7.33 (1H, dd, J = 7.5,1Hz), 7.62 (1H, d,
J = 7.5Hz), 7.90 (1H, d, J = 1Hz), 7.97 (1H, d, J = 7.5Hz) MASS (m / z): 461 (M+ +1), 459 (M+ ), 76 (bp)
【０２５６】(11) １−（２−クロロベンジル）−３−
シアノ−２−プロピルインドール−６−カルボキサミド mp : 222−223.5℃ IR (KBr) : 3443, 3183, 2215, 1679, 1394 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.70 (2H,sexte
t,J=7Hz), 2.89 (2H,t,J=7.5Hz), 5.50 (2H,s), 6.21
(1H,d,J=7.5Hz), 7.08 (1H,t,J=7.5Hz),7.24 (1H,ddd,J
=7.5, 7.5, 1Hz), 7.47 (1H,d,J=7.5Hz), 7.61 (1H,d,J
=7.5Hz), 7.77 (1H,d,J=7.5Hz), 7.89 (1H,d,J=1Hz) MASS (m/z) : 352 (M++1), 76 (bp) (12) １−（２−クロロベンジル）−２−エチル−３−
イソブチリルインドール−６−カルボキサミド mp : 178−180.5℃ NMR (CDCl3,δ) : 1.22 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 3.09 (2H,q,J=7Hz), 3.56 (1H,m), 5.51 (2H,s),
6.22 (1H,d,J=8Hz), 7.04 (1H,t,J=8Hz), 7.22 (1H,t,J
=8Hz), 7.44 (1H,d,J=8Hz), 7.63 (1H,d,J=8Hz),J=8H
z), 7.82 (1H,s), 7.98 (1H,d,J=8Hz)(11) 1- (2-chlorobenzyl) -3-
Cyano-2-propylindole-6-carboxamide mp: 222-223.5 ° C IR (KBr): 3443, 3183, 2215, 1679, 1394 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz ), 1.70 (2H, sexte
(t, J = 7Hz), 2.89 (2H, t, J = 7.5Hz), 5.50 (2H, s), 6.21
(1H, d, J = 7.5Hz), 7.08 (1H, t, J = 7.5Hz), 7.24 (1H, ddd, J
= 7.5, 7.5, 1Hz), 7.47 (1H, d, J = 7.5Hz), 7.61 (1H, d, J
= 7.5Hz), 7.77 (1H, d, J = 7.5Hz), 7.89 (1H, d, J = 1Hz) MASS (m / z): 352 (M+ +1), 76 (bp) (12) 1 -(2-chlorobenzyl) -2-ethyl-3-
Isobutyryl-indole-6-carboxamidemp: 178-180.5 ℃ NMR (CDCl 3 , δ): 1.22 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 3.09 (2H, q, J = 7Hz), 3.56 (1H, m), 5.51 (2H, s),
6.22 (1H, d, J = 8Hz), 7.04 (1H, t, J = 8Hz), 7.22 (1H, t, J
= 8Hz), 7.44 (1H, d, J = 8Hz), 7.63 (1H, d, J = 8Hz), J = 8H
z), 7.82 (1H, s), 7.98 (1H, d, J = 8Hz)
【０２５７】(13) １−（２−クロロベンジル）−３−
イソブチリル−２−メチルインドール−６−カルボキサ
ミド mp : 212−215℃ NMR (CDCl3,δ) : 1.30 (6H,d,J=7Hz), 2.69 (3H,s),
3.53 (1H,m), 5.48(2H,s), 6.21 (1H,d,J=8Hz), 7.04
(1H,t,J=8Hz), 7.23 (1H,t,J=8Hz),7.45 (1H,d,J=8Hz),
7.62 (1H,d,J=8Hz), 7.87 (1H,s), 8.03 (1H,d,J=8Hz) (14) １−（２−クロロベンジル）−３−イソブチリル
−２−メトキシメチルインドール−６−カルボキサミド mp : 204−206℃ NMR (CDCl3,δ) : 1.32 (6H,d,J=7Hz), 3.34 (3H,s),
3.57 (1H,m), 4.92(2H,s), 5.65 (2H,s), 6.24 (1H,d,J
=8Hz), 7.03 (1H,t,J=8Hz), 7.21(1H,t,J=8Hz), 7.44
(1H,d,J=8Hz), 7.67 (1H,d,J=8Hz), 7.83 (1H,s),8.02
(1H,d,J=8Hz)(13) 1- (2-chlorobenzyl) -3-
Isobutyryl-2-methylindole-6-carboxamide mp: 212-215 ° C NMR (CDCl3 , δ): 1.30 (6H, d, J = 7Hz), 2.69 (3H, s),
3.53 (1H, m), 5.48 (2H, s), 6.21 (1H, d, J = 8Hz), 7.04
(1H, t, J = 8Hz), 7.23 (1H, t, J = 8Hz), 7.45 (1H, d, J = 8Hz),
7.62 (1H, d, J = 8Hz), 7.87 (1H, s), 8.03 (1H, d, J = 8Hz) (14) 1- (2-chlorobenzyl) -3-isobutyryl-2-methoxymethylindole- 6-carboxamide mp: 204-206 ° C NMR (CDCl3 , δ): 1.32 (6H, d, J = 7Hz), 3.34 (3H, s),
3.57 (1H, m), 4.92 (2H, s), 5.65 (2H, s), 6.24 (1H, d, J
= 8Hz), 7.03 (1H, t, J = 8Hz), 7.21 (1H, t, J = 8Hz), 7.44
(1H, d, J = 8Hz), 7.67 (1H, d, J = 8Hz), 7.83 (1H, s), 8.02
(1H, d, J = 8Hz)
【０２５８】(15) １−（２−クロロベンジル）−３−
イソブチリルインドール−６−カルボキサミド mp : 235−237℃ NMR (DMSO-d6,δ) : 1.16 (6H,d,J=7Hz), 3.40 (1H,m),
5.67 (2H,s), 6.70(1H,d,J=8Hz), 7.2-7.4 (3H,m), 7.
56 (1H,d,J=8Hz), 7.80 (1H,d,J=8Hz), 7.96 (1H,br
s), 8.04 (1H,s), 8.27 (1H,d,J=8Hz), 8.64 (1H,s) (16) ３−イソブチリル−２−プロピル−１−（２−ピ
リジルメチル）インドール−６−カルボキサミド NMR (DMSO-d6,δ) : 0.90 (3H,t,J=7Hz), 1.17 (6H,d,J
=7Hz), 1.46 (2H,sextet,J=7Hz), 3.08-3.15 (2H,m),
3.52 (2H,septet,J=7Hz), 5.66(2H,s), 7.08 (1H,d,J=8
Hz), 7.28-7.32 (2H,m), 7.78 (1H,d,J=8Hz),7.92 (1H,
d,J=8Hz), 8.09 (1H,s), 8.50 (1H,d,J=5Hz)(15) 1- (2-chlorobenzyl) -3-
Isobutyrylindole-6-carboxamide mp: 235-237 ° C NMR (DMSO-d6 , δ): 1.16 (6H, d, J = 7Hz), 3.40 (1H, m),
5.67 (2H, s), 6.70 (1H, d, J = 8Hz), 7.2-7.4 (3H, m), 7.
56 (1H, d, J = 8Hz), 7.80 (1H, d, J = 8Hz), 7.96 (1H, br
s), 8.04 (1H, s), 8.27 (1H, d, J = 8Hz), 8.64 (1H, s) (16) 3-isobutyryl-2-propyl-1- (2-pyridylmethyl) indole-6 Carboxamide NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 7Hz), 1.17 (6H, d, J
= 7Hz), 1.46 (2H, sextet, J = 7Hz), 3.08-3.15 (2H, m),
3.52 (2H, septet, J = 7Hz), 5.66 (2H, s), 7.08 (1H, d, J = 8
Hz), 7.28-7.32 (2H, m), 7.78 (1H, d, J = 8Hz), 7.92 (1H,
d, J = 8Hz), 8.09 (1H, s), 8.50 (1H, d, J = 5Hz)
【０２５９】(17) １−（２−クロロベンジル）−２,３
−ジエチルインドール−６−カルボキサミド mp : 185−187.5℃ IR (KBr) : 3400, 1650, 1610 cm-1 NMR (CDCl3,δ) : 1.15 (3H,t,J=7Hz), 1.29 (3H,t,J=7
Hz), 2.69 (2H,q,J=7Hz), 2.80 (2H,q,J=7Hz), 5.44 (2
H,s), 6.17 (1H,d,J=7.5Hz), 7.00(1H,t,J=7.5Hz), 7.1
8 (1H,t,J=7.5Hz), 7.41 (1H,d,J=7.5Hz), 7.47(1H,d,J
=7.5Hz), 7.62 (1H,d,J=7.5Hz), 7.76 (1H,s) MASS (m/z) : 341 (M++1), 76 (bp) (18) ３−アセチル−１−（２−クロロベンジル）−２
−エチルインドール−６−カルボキサミド mp : 217−220℃ NMR (CDCl3,δ) : 1.22 (3H,t,J=7Hz), 2.73 (3H,s),
3.12 (2H,q,J=7Hz),5.49 (2H,s), 6.20 (1H,d,J=8Hz),
7.02 (1H,t,J=8Hz), 7.22 (1H,t,J=8Hz), 7.43 (1H,d,J
=8Hz), 7.63 (1H,d,J=8Hz), 7.83 (1H,s), 8.08(1H,d,J
=8Hz)(17) 1- (2-chlorobenzyl) -2,3
-Diethylindole-6-carboxamide mp: 185-187.5 ° C IR (KBr): 3400, 1650, 1610 cm-1 NMR (CDCl3 , δ): 1.15 (3H, t, J = 7Hz), 1.29 (3H, t , J = 7
Hz), 2.69 (2H, q, J = 7Hz), 2.80 (2H, q, J = 7Hz), 5.44 (2
H, s), 6.17 (1H, d, J = 7.5Hz), 7.00 (1H, t, J = 7.5Hz), 7.1
8 (1H, t, J = 7.5Hz), 7.41 (1H, d, J = 7.5Hz), 7.47 (1H, d, J
= 7.5Hz), 7.62 (1H, d, J = 7.5Hz), 7.76 (1H, s) MASS (m / z): 341 (M+ +1), 76 (bp) (18) 3-acetyl-1 -(2-chlorobenzyl) -2
-Ethylindole-6-carboxamide mp: 217-220 ° C NMR (CDCl3 , δ): 1.22 (3H, t, J = 7Hz), 2.73 (3H, s),
3.12 (2H, q, J = 7Hz), 5.49 (2H, s), 6.20 (1H, d, J = 8Hz),
7.02 (1H, t, J = 8Hz), 7.22 (1H, t, J = 8Hz), 7.43 (1H, d, J
= 8Hz), 7.63 (1H, d, J = 8Hz), 7.83 (1H, s), 8.08 (1H, d, J
= 8Hz)
【０２６０】(19) １−（２−クロロベンジル）−３−
ホルミル−２−プロピルインドール−６−カルボキサミ
ド mp : 245℃ (分解) NMR (DMSO-d6,δ) : 0.92 (3H,t,J=7Hz), 1.63 (2H,m),
3.11 (2H,t,J=7Hz),5.64 (2H,s), 6.32 (1H,d,J=8Hz),
7.21 (1H,t,J=8Hz), 7.25-7.35 (2H,m), 7.60 (1H,d,J
=8Hz), 7.83 (1H,d,J=8Hz), 7.95 (1H,d,J=8Hz), 7.97
(1H,s), 8.21 (1H,d,J=8Hz), >10 (1H,s)(19) 1- (2-chlorobenzyl) -3-
Formyl-2-propylindole-6-carboxamide mp: 245 ° C. (decomposition) NMR (DMSO-d6 , δ): 0.92 (3H, t, J = 7Hz), 1.63 (2H, m),
3.11 (2H, t, J = 7Hz), 5.64 (2H, s), 6.32 (1H, d, J = 8Hz),
7.21 (1H, t, J = 8Hz), 7.25-7.35 (2H, m), 7.60 (1H, d, J
= 8Hz), 7.83 (1H, d, J = 8Hz), 7.95 (1H, d, J = 8Hz), 7.97
(1H, s), 8.21 (1H, d, J = 8Hz),> 10 (1H, s)
【０２６１】製造例91 製造例87−(11)、製造例87−(20)または製造例87−(21)
で得た化合物(Ｉ−２)から、製造例59と同様にして、下
記(1)〜(3)に記載の化合物を製造した。 (1) ３−ベンゾイル−１−（２−クロロベンジル）−２
−プロピルインドール−６−カルボキサミド NMR (DMSO-d6,δ) : 0.78 (3H,t,J=8Hz), 1.46 (2H,sex
tet,J=8Hz), 2.88(2H,t,J=8Hz), 5.66 (2H,s), 6.33 (1
H,dd,J=1, 8Hz), 7.08 (1H,dt,J=1, 8Hz), 7.20-7.38
(3H,m), 7.52-7.72 (7H,m), 7.88 (1H,br s),7.99 (1H,
s) (2) １−（２−クロロベンジル）−３−フェニルアセチ
ル−２−プロピルインドール−６−カルボキサミド NMR (DMSO-d6,δ) : 0.88 (3H,t,J=8Hz), 1.47 (2H,sex
tet,J=8Hz), 2.98-3.03 (2H,m), 4.42 (2H,s), 5.63 (2
H,s), 6.20 (1H,d,J=8Hz), 7.17(1H,t,J=8Hz), 7.24-7.
35 (6H,m), 7.57 (1H,d,J=8Hz), 7.82 (1H,d,J=8Hz),
7.95 (1H,br s), 8.02 (1H,s), 8.14 (1H,d,J=8Hz)Production Example 91 Production Example 87- (11), Production Example 87- (20) or Production Example 87- (21)
The following compounds (1) to (3) were produced in the same manner as in Production Example 59 from the compound (I-2) obtained in (1). (1) 3-benzoyl-1- (2-chlorobenzyl) -2
- propyl indole-6-carboxamideNMR (DMSO-d 6, δ ): 0.78 (3H, t, J = 8Hz), 1.46 (2H, sex
tet, J = 8Hz), 2.88 (2H, t, J = 8Hz), 5.66 (2H, s), 6.33 (1
H, dd, J = 1,8Hz), 7.08 (1H, dt, J = 1,8Hz), 7.20-7.38
(3H, m), 7.52-7.72 (7H, m), 7.88 (1H, br s), 7.99 (1H,
s) (2) 1- (2-chlorobenzyl) -3-phenylacetyl-2-propylindole-6-carboxamide NMR (DMSO-d6 , δ): 0.88 (3H, t, J = 8Hz), 1.47 ( 2H, sex
tet, J = 8Hz), 2.98-3.03 (2H, m), 4.42 (2H, s), 5.63 (2
H, s), 6.20 (1H, d, J = 8Hz), 7.17 (1H, t, J = 8Hz), 7.24-7.
35 (6H, m), 7.57 (1H, d, J = 8Hz), 7.82 (1H, d, J = 8Hz),
7.95 (1H, br s), 8.02 (1H, s), 8.14 (1H, d, J = 8Hz)
【０２６２】(3) ３−アセチル−１−（６−クロロ−
３,４−メチレンジオキシベンジル）−２−プロピルイ
ンドール−６−カルボキサミド mp : 220−223℃ NMR (DMSO-d6,δ) : 0.94 (3H,t,J=8Hz), 1.50 (2H,sex
tet,J=8Hz), 2.65(3H,s), 3.02-3.06 (2H,m), 5.52 (2
H,s), 5.66 (1H,s), 5.99 (2H,s),7.23 (1H,s), 7.86
(1H,d,J=8Hz), 8.01 (1H,s), 8.05 (1H,d,J=8Hz)(3) 3-acetyl-1- (6-chloro-
3,4-methylenedioxybenzyl) -2-propylindole-6-carboxamide mp: 220-223 ° C NMR (DMSO-d6 , δ): 0.94 (3H, t, J = 8Hz), 1.50 (2H, sex
tet, J = 8Hz), 2.65 (3H, s), 3.02-3.06 (2H, m), 5.52 (2
H, s), 5.66 (1H, s), 5.99 (2H, s), 7.23 (1H, s), 7.86
(1H, d, J = 8Hz), 8.01 (1H, s), 8.05 (1H, d, J = 8Hz)
【０２６３】製造例92 ３−イソブチリル−２−プロピル−１−（２−ピリジル
メチル）インドール−６−カルボキシアミド（80mg）の
クロロホルム（２ml）溶液に、１Ｍ塩化水素−メタノー
ル溶液（１ml）を25℃で加え、混合物を15分間撹拌し
た。溶媒を蒸発させたのち、残留物をエタノール−酢酸
エチル混合物から結晶化させて、３−イソブチリル−２
−プロピル−１−（２−ピリジルメチル）インドール−
６−カルボキシアミド塩酸塩（80mg）を無色結晶として
得た。 mp : 230−235℃ NMR (DMSO-d6,δ) : 0.92 (3H,t,J=7Hz), 1.17 (6H,d,J
=7Hz), 1.45 (2H,sextet,J=7Hz), 3.08-3.14 (2H,m),
3.52 (2H,septet,J=7Hz), 5.74(2H,s), 7.09 (1H,d,J=8
Hz), 7.46 (1H,dd,J=5, 8Hz), 7.79 (1H,d,J=8Hz), 7.9
0 (1H,d,J=8Hz), 7.92 (1H,t,J=8Hz), 8.12 (1H,s), 8.
62(1H,d,J=5Hz)Production Example 92 To a solution of 3-isobutyryl-2-propyl-1- (2-pyridylmethyl) indole-6-carboxamide (80 mg) in chloroform (2 ml) was added 25 ml of a 1M hydrogen chloride-methanol solution (1 ml). C. and the mixture was stirred for 15 minutes. After evaporation of the solvent, the residue is crystallized from an ethanol-ethyl acetate mixture to give 3-isobutyryl-2.
-Propyl-1- (2-pyridylmethyl) indole-
6-Carboxamide hydrochloride (80 mg) was obtained as colorless crystals. mp: 230-235 ° C NMR (DMSO-d6 , δ): 0.92 (3H, t, J = 7Hz), 1.17 (6H, d, J
= 7Hz), 1.45 (2H, sextet, J = 7Hz), 3.08-3.14 (2H, m),
3.52 (2H, septet, J = 7Hz), 5.74 (2H, s), 7.09 (1H, d, J = 8
Hz), 7.46 (1H, dd, J = 5,8Hz), 7.79 (1H, d, J = 8Hz), 7.9
0 (1H, d, J = 8Hz), 7.92 (1H, t, J = 8Hz), 8.12 (1H, s), 8.
62 (1H, d, J = 5Hz)
【０２６４】製造例93 ３−イソブチリル−１−（２−メトキシカルボニルベン
ジル）−２−プロピルインドール−６−カルボキサミド
（265mg）から、製造例55と同様にして、１−（２−カ
ルボキシベンジル）−３−イソブチリル−２−プロピル
インドール−６−カルボキサミド（242mg）を製造し
た。 mp : 268−269℃ (分解) IR (KBr) : 1740, 1690, 1625, 1620 cm-1 NMR (DMSO-d6,δ) : 0.90 (3H,t,J=7Hz), 1.19 (6H,d,J
=7Hz), 1.42-1.51(2H,m), 2.94-3.06 (2H,m), 3.50-3.6
0 (1H,m), 5.96 (2H,s), 6.06-6.10 (1H,m), 7.37-7.40
(2H,m), 7.79-7.82 (1H,m), 7.91-7.95 (1H,m), 7.99
(1H,s), 8.03-8.06 (1H,m) MASS (m/z) : 407 (M++1), 86 (bp)Production Example 93 From 3-isobutyryl-1- (2-methoxycarbonylbenzyl) -2-propylindole-6-carboxamide (265 mg), 1- (2-carboxybenzyl)- 3-isobutyryl-2-propylindole-6-carboxamide (242 mg) was prepared. mp: 268-269 ° C (decomposition) IR (KBr): 1740, 1690, 1625, 1620 cm-1 NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 7Hz), 1.19 (6H, d , J
= 7Hz), 1.42-1.51 (2H, m), 2.94-3.06 (2H, m), 3.50-3.6
0 (1H, m), 5.96 (2H, s), 6.06-6.10 (1H, m), 7.37-7.40
(2H, m), 7.79-7.82 (1H, m), 7.91-7.95 (1H, m), 7.99
(1H, s), 8.03-8.06 (1H, m) MASS (m / z): 407 (M+ +1), 86 (bp)
【０２６５】製造例94 １−（２−カルボキシベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボキサミド（164m
g）から、製造例56と同様にして、１−（２−カルバモ
イルベンジル）−３−イソブチリル−２−プロピルイン
ドール−６−カルボキサミド（102mg）を製造した。 mp : 273−274℃ IR (KBr) : 1690 cm-1 NMR (DMSO-d6,δ) : 0.91 (3H,t,J=7Hz), 1.19 (6H,d,J
=7Hz), 1.41-1.51(2H,m), 2.94-2.99 (2H,m), 3.48-3.5
7 (1H,m), 5.79 (2H,s), 6.17(1H,d,J=7.5Hz), 7.22-7.
35 (3H,m), 7.61-7.68 (2H,m), 7.80 (1H,d,J=7.5Hz),
7.92-7.97 (2H,m), 8.04 (1H,s), 8.13 (1H,s) MASS (m/z) : 406 (M++1), 87 (bp)Production Example 94 1- (2-carboxybenzyl) -3-isobutyryl-
2-propylindole-6-carboxamide (164m
From g), 1- (2-carbamoylbenzyl) -3-isobutyryl-2-propylindole-6-carboxamide (102 mg) was produced in the same manner as in Production Example 56. mp: 273-274 ° C IR (KBr): 1690 cm-1 NMR (DMSO-d6 , δ): 0.91 (3H, t, J = 7Hz), 1.19 (6H, d, J
= 7Hz), 1.41-1.51 (2H, m), 2.94-2.99 (2H, m), 3.48-3.5
7 (1H, m), 5.79 (2H, s), 6.17 (1H, d, J = 7.5Hz), 7.22-7.
35 (3H, m), 7.61-7.68 (2H, m), 7.80 (1H, d, J = 7.5Hz),
7.92-7.97 (2H, m), 8.04 (1H, s), 8.13 (1H, s) MASS (m / z): 406 (M+ +1), 87 (bp)
【０２６６】製造例95 オキシ塩化燐（0.031ml）のジメチルホルムアミド（1.2
ml）溶液に、０℃で、１−（２−クロロベンジル）−２
−エチル−３−プロピオニルインドール−６−カルボキ
サミド（112mg）を加え、混合物を15分間撹拌した。生
じた混合物をアンモニア水と氷との中に注ぎ、つぎに酢
酸エチルで抽出した。有機層を食塩水で洗い、硫酸ナト
リウムで乾燥し、減圧下で蒸発させた。残留物をヘキサ
ン−イソプロピルエーテル混合物を用いて粉末化して、
１−（２−クロロベンジル）−２−エチル−３−プロピ
オニルインドール−６−カルボニトリル（93mg）を固体
として得た。 mp : 115−118℃ NMR (CDCl3,δ) : 1.25 (3H,t,J=7Hz), 1.30 (3H,t,J=7
Hz), 3.09 (2H,q,J=7Hz), 3.17 (2H,q,J=7Hz), 5.47 (2
H,s), 6.21 (1H,d,J=8Hz), 7.07(1H,t,J=8Hz), 7.25 (1
H,t,J=8Hz), 7.45-7.55 (3H,m), 8.09 (1H,d,J=7Hz)Production Example 95 Phosphorus oxychloride (0.031 ml) in dimethylformamide (1.2
ml) solution at 0 ° C. with 1- (2-chlorobenzyl) -2
-Ethyl-3-propionylindole-6-carboxamide (112 mg) was added and the mixture was stirred for 15 minutes. The resulting mixture was poured into aqueous ammonia and ice, and then extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue is triturated with a hexane-isopropyl ether mixture,
1- (2-Chlorobenzyl) -2-ethyl-3-propionylindole-6-carbonitrile (93 mg) was obtained as a solid. mp: 115-118 ° C NMR (CDCl3 , δ): 1.25 (3H, t, J = 7Hz), 1.30 (3H, t, J = 7
Hz), 3.09 (2H, q, J = 7Hz), 3.17 (2H, q, J = 7Hz), 5.47 (2
H, s), 6.21 (1H, d, J = 8Hz), 7.07 (1H, t, J = 8Hz), 7.25 (1
(H, t, J = 8Hz), 7.45-7.55 (3H, m), 8.09 (1H, d, J = 7Hz)
【０２６７】製造例96 １−（２−クロロベンジル）−２−エチル−３−イソブ
チリルインドール−６−カルボキサミド（280mg）か
ら、製造例95と同様にして、１−（２−クロロベンジ
ル）−２−エチル−３−イソブチリルインドール−６−
カルボニトリル(239mg)を製造した。 mp : 132−134℃ NMR (CDCl3,δ) : 1.23 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 3.13 (2H,q,J=7Hz), 3.50 (1H,m), 5.48 (2H,s),
6.22 (1H,d,J=8Hz), 7.07 (1H,t,J=8Hz), 7.27 (1H,t,J
=8Hz), 7.27 (1H,d,J=8Hz), 7.44-7.53 (2H,m),8.02 (1
H,d,J=8Hz)Production Example 96 From 1- (2-chlorobenzyl) -2-ethyl-3-isobutyrylindole-6-carboxamide (280 mg), 1- (2-chlorobenzyl) was prepared in the same manner as in Production Example 95. -2-ethyl-3-isobutyrylindole-6
Carbonitrile (239 mg) was produced. mp: 132-134 ° C NMR (CDCl3 , δ): 1.23 (3H, t, J = 7Hz), 1.31 (6H, d, J = 7
Hz), 3.13 (2H, q, J = 7Hz), 3.50 (1H, m), 5.48 (2H, s),
6.22 (1H, d, J = 8Hz), 7.07 (1H, t, J = 8Hz), 7.27 (1H, t, J
= 8Hz), 7.27 (1H, d, J = 8Hz), 7.44-7.53 (2H, m), 8.02 (1
(H, d, J = 8Hz)
【０２６８】製造例97 １−（２−クロロベンジル）−２−エチル−３−プロピ
オニルインドール−６−カルボニトリル（107mg）のキ
シレン（５ml）溶液に、アジ化トリメチルスズ（190m
g）を加え、混合物を120℃で14時間撹拌する。生じた混
合物を１Ｎ塩酸中に注ぎ、酢酸エチルで抽出した。有機
層を食塩水で洗い、硫酸ナトリウムで乾燥し、減圧下で
蒸発させた。残留物をシリカゲルクロマトグラフィーに
付し、20％メタノール−クロロホルム溶液で溶出して、
１−（２−クロロベンジル）−２−エチル−３−プロピ
オニル−６−（１Ｈ−テトラゾール−５−イル）インド
ール（77mg）を固体として得た。 mp : 178−181℃ NMR (CDCl3,δ) : 1.18 (3H,t,J=7Hz), 1.34 (3H,t,J=7
Hz), 3.0-3.15 (4H,m), 5.42 (2H,s), 6.21 (1H,d,J=8H
z), 6.94 (1H,t,J=8Hz), 7.13 (1H,t,J=8Hz), 7.33 (1
H,d,J=8Hz), 8.03 (1H,d,J=8Hz), 8.05 (1H,s), 8.25(1
H,d,J=8Hz)Production Example 97 To a solution of 1- (2-chlorobenzyl) -2-ethyl-3-propionylindole-6-carbonitrile (107 mg) in xylene (5 ml) was added trimethyltin azide (190 ml).
g) is added and the mixture is stirred at 120 ° C. for 14 hours. The resulting mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with a 20% methanol-chloroform solution,
1- (2-Chlorobenzyl) -2-ethyl-3-propionyl-6- (1H-tetrazol-5-yl) indole (77 mg) was obtained as a solid. mp: 178-181 ° C NMR (CDCl3 , δ): 1.18 (3H, t, J = 7Hz), 1.34 (3H, t, J = 7
Hz), 3.0-3.15 (4H, m), 5.42 (2H, s), 6.21 (1H, d, J = 8H
z), 6.94 (1H, t, J = 8Hz), 7.13 (1H, t, J = 8Hz), 7.33 (1
H, d, J = 8Hz), 8.03 (1H, d, J = 8Hz), 8.05 (1H, s), 8.25 (1
(H, d, J = 8Hz)
【０２６９】製造例98 １−（２−クロロベンジル）−２−エチル−３−イソブ
チリルインドール−６−カルボニトリル（130mg）か
ら、製造例97と同様にして、１−（２−クロロベンジ
ル）−２−エチル−３−イソブチリル−６−（１Ｈ−テ
トラゾール−５−イル）インドール（109mg）を製造し
た。 mp : 160−163℃ NMR (CDCl3,δ) : 1.18 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 3.04 (2H,q,J=7Hz), 3.52 (1H,m), 5.37 (2H,s),
6.20 (1H,d,J=8Hz), 6.94 (1H,t,J=8Hz), 7.11 (1H,t,J
=8Hz), 7.33 (1H,d,J=8Hz), 8.00 (1H,d,J=8Hz),8.02
(1H,s), 8.13 (1H,d,J=8Hz)Production Example 98 From 1- (2-chlorobenzyl) -2-ethyl-3-isobutyrylindole-6-carbonitrile (130 mg), 1- (2-chlorobenzyl) ) -2-Ethyl-3-isobutyryl-6- (1H-tetrazol-5-yl) indole (109 mg) was prepared. mp: 160-163 ° C NMR (CDCl3 , δ): 1.18 (3H, t, J = 7Hz), 1.31 (6H, d, J = 7
Hz), 3.04 (2H, q, J = 7Hz), 3.52 (1H, m), 5.37 (2H, s),
6.20 (1H, d, J = 8Hz), 6.94 (1H, t, J = 8Hz), 7.11 (1H, t, J
= 8Hz), 7.33 (1H, d, J = 8Hz), 8.00 (1H, d, J = 8Hz), 8.02
(1H, s), 8.13 (1H, d, J = 8Hz)
【０２７０】製造例99 製造例30と同様にして、下記(1)〜(2)に記載の化合物を
製造した。 (1) ２−（３−カルボキシプロピル）−１−（２−クロ
ロベンジル）インドール−６−カルボン酸メチルエステ
ル NMR (CDCl3,δ) : 2.04 (2H,m), 2.45 (2H,t,J=7Hz),
2.73 (2H,t,J=7Hz),3.89 (3H,s), 5.44 (2H,s), 6.14
(1H,d,J=8Hz), 6.47 (1H,s), 7.01(1H,t,J=8Hz), 7.18
(1H,t,J=8Hz), 7.44 (1H,d,J=8Hz), 7.62 (1H,d,J=8H
z), 7.83 (1H,d,J=8Hz), 7.93 (1H,s) (2) ２−（２−カルボキシエチル）−１−（２−クロロ
ベンジル）インドール−６−カルボン酸エステル NMR (CDCl3,δ) : 2.76 (2H,t,J=7Hz), 2.96 (2H,t,J=7
Hz), 3.88 (3H,s),5.46 (2H,s), 6.16 (1H,d,J=8Hz),
6.46 (1H,s), 7.01 (1H,t,J=8Hz),7.20 (1H,t,J=8Hz),
7.43 (1H,d,J=8Hz), 7.62 (1H,d,J=8Hz), 7.82(1H,d,J=
8Hz), 7.93 (1H,s)Production Example 99 In the same manner as in Production Example 30, the following compounds (1) and (2) were produced. (1) 2- (3-carboxypropyl) -1- (2-chlorobenzyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.04 (2H, m), 2.45 (2H, t, J = 7Hz),
2.73 (2H, t, J = 7Hz), 3.89 (3H, s), 5.44 (2H, s), 6.14
(1H, d, J = 8Hz), 6.47 (1H, s), 7.01 (1H, t, J = 8Hz), 7.18
(1H, t, J = 8Hz), 7.44 (1H, d, J = 8Hz), 7.62 (1H, d, J = 8H)
z), 7.83 (1H, d, J = 8 Hz), 7.93 (1H, s) (2) 2- (2-carboxyethyl) -1- (2-chlorobenzyl) indole-6-carboxylic acid ester NMR (CDCl3 , δ): 2.76 (2H, t, J = 7Hz), 2.96 (2H, t, J = 7
Hz), 3.88 (3H, s), 5.46 (2H, s), 6.16 (1H, d, J = 8Hz),
6.46 (1H, s), 7.01 (1H, t, J = 8Hz), 7.20 (1H, t, J = 8Hz),
7.43 (1H, d, J = 8Hz), 7.62 (1H, d, J = 8Hz), 7.82 (1H, d, J =
8Hz), 7.93 (1H, s)
【０２７１】製造例100 製造例31と同様にして、下記(1)〜(2)に記載の化合物を
製造した。 (1) ９−（２−クロロベンジル）−５−オキソ−５,６,
７,８−テトラヒドロカルバゾール−２−カルボン酸メ
チルエステル NMR (CDCl3,δ) : 2.24 (2H,m), 2.62 (2H,t,J=7Hz),
2.86 (2H,t,J=7Hz),3.90 (3H,s), 5.47 (2H,s), 6.34
(1H,d,J=8Hz), 7.09 (1H,t,J=8Hz),7.25 (1H,t,J=8Hz),
7.47 (1H,d,J=8Hz), 7.97 (1H,s), 7.99 (1H,d,J=8H
z), 8.33 (1H,d,J=8Hz) (2) ４−（２−クロロベンジル）−１−オキソ−１,２,
３,４−テトラヒドロシクロペンタ［ｂ］インドール−
６−カルボン酸メチルエステル NMR (CDCl3,δ) : 2.9-3.15 (4H,m), 3.91 (3H,s), 5.4
6 (2H,s), 6.66 (1H,d,J=8Hz), 7.17 (1H,t,J=8Hz), 7.
29 (1H,t,J=8Hz), 7.48 (1H,d,J=8Hz),7.94-8.06 (3H,
m)Production Example 100 In the same manner as in Production Example 31, the following compounds (1) and (2) were produced. (1) 9- (2-chlorobenzyl) -5-oxo-5,6,
7,8-tetrahydrocarbazole-2-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.24 (2H, m), 2.62 (2H, t, J = 7Hz),
2.86 (2H, t, J = 7Hz), 3.90 (3H, s), 5.47 (2H, s), 6.34
(1H, d, J = 8Hz), 7.09 (1H, t, J = 8Hz), 7.25 (1H, t, J = 8Hz),
7.47 (1H, d, J = 8Hz), 7.97 (1H, s), 7.99 (1H, d, J = 8H
z), 8.33 (1H, d, J = 8Hz) (2) 4- (2-chlorobenzyl) -1-oxo-1,2,
3,4-tetrahydrocyclopenta [b] indole-
6-Carboxylic acid methyl ester NMR (CDCl3 , δ): 2.9-3.15 (4H, m), 3.91 (3H, s), 5.4
6 (2H, s), 6.66 (1H, d, J = 8Hz), 7.17 (1H, t, J = 8Hz), 7.
29 (1H, t, J = 8Hz), 7.48 (1H, d, J = 8Hz), 7.94-8.06 (3H,
m)
【０２７２】製造例101 製造例１−(5)と同様にして、下記(1)〜(2)に記載の化
合物を製造した。 (1) ３−クロロアセチル−１−（２−クロロベンジル）
−２−プロピルインドール−６−カルボン酸メチルエス
テル mp : 143−145℃ IR (KBr) : 1722, 1666 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.55-1.66 (2H,
m), 3.05-3.10 (2H,m), 3.91 (3H,s), 4.82 (2H,s), 5.
53 (2H,s), 6.25 (1H,d,J=7.5Hz),7.05 (1H,t,J=7.5H
z), 7.20-7.25 (1H,m), 7.49 (1H,d,J=7.5Hz), 7.88(1
H,d,J=8Hz), 7.98 (1H,s), 8.00 (1H,d,J=8Hz) MASS (m/z) : 418 (M+-1), 76 (bp) (2) １−（２−クロロベンジル）−３−クロトノイル−
２−プロピルインドール−６−カルボキサミド mp : 185.5−186.5℃ IR (KBr) : 1648, 1614, 1443, 1414, 1388 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.64 (2H,sexte
t,J=7Hz), 2.04 (3H,d,J=7Hz), 3.00 (2H,t,J=7Hz), 5.
51 (2H,s), 6.24 (1H,d,J=8Hz), 6.92(1H,d,J=15Hz),
7.00-7.06 (2H,m), 7.23 (1H,t,J=8Hz), 7.46 (1H,d,J=
7.5Hz), 7.60 (1H,d,J=7.5Hz), 7.83 (1H,s), 7.99 (1
H,d,J=8Hz) MASS (m/z) : 395 (M++1), 74 (bp)Production Example 101 The following compounds (1) and (2) were produced in the same manner as in Production Example 1- (5). (1) 3-chloroacetyl-1- (2-chlorobenzyl)
-2-Propylindole-6-carboxylic acid methyl ester mp: 143-145 ° C IR (KBr): 1722, 1666 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.55- 1.66 (2H,
m), 3.05-3.10 (2H, m), 3.91 (3H, s), 4.82 (2H, s), 5.
53 (2H, s), 6.25 (1H, d, J = 7.5Hz), 7.05 (1H, t, J = 7.5H
z), 7.20-7.25 (1H, m), 7.49 (1H, d, J = 7.5Hz), 7.88 (1
H, d, J = 8Hz), 7.98 (1H, s), 8.00 (1H, d, J = 8Hz) MASS (m / z): 418 (M+ -1), 76 (bp) (2) 1- (2-chlorobenzyl) -3-crotonoyl-
2-propylindole-6-carboxamide mp: 185.5-186.5 ° C IR (KBr): 1648, 1614, 1443, 1414, 1388 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.64 (2H, sexte
(t, J = 7Hz), 2.04 (3H, d, J = 7Hz), 3.00 (2H, t, J = 7Hz), 5.
51 (2H, s), 6.24 (1H, d, J = 8Hz), 6.92 (1H, d, J = 15Hz),
7.00-7.06 (2H, m), 7.23 (1H, t, J = 8Hz), 7.46 (1H, d, J =
7.5Hz), 7.60 (1H, d, J = 7.5Hz), 7.83 (1H, s), 7.99 (1
H, d, J = 8Hz) MASS (m / z): 395 (M+ +1), 74 (bp)
【０２７３】製造例102 ３−クロロアセチル−１−（２−クロロベンジル）−２
−プロピルインドール−６−カルボン酸メチルエステル
（123mg）とモルホリン（１ml）とからなる混合物を、5
0℃で2.5時間撹拌した。20℃まで冷却後、反応混合物を
酢酸エチルで抽出した。有機層を１Ｎ塩酸および水で洗
い、硫酸マグネシウムで乾燥し、減圧下で蒸発させた。
残留物をシリカゲルクロマトグラフィーに付し、酢酸エ
チル−ヘキサン（１：２）混合物で溶出して、１−（２
−クロロベンジル）−３−モルホリノアセチル−２−プ
ロピルインドール−６−カルボン酸メチルエステル（94
mg）を無色無定形物として得た。 IR (KBr) : 1712, 1657 cm-1 NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.60-1.65 (2H,
m), 2.70-2.75 (4H,m), 3.06 (2H,t,J=7Hz), 3.84 (4H,
t,J=7Hz), 3.90 (2H,s), 3.92 (3H,s), 5.52 (2H,s),
6.24 (1H,d,J=7.5Hz), 7.06 (1H,t,J=7.5Hz), 7.24(1H,
t,J=7.5Hz), 7.48 (1H,d,J=7.5Hz), 7.94-7.98 (3H,m) MASS (m/z) : 469 (M++1)Production Example 102 3-Chloroacetyl-1- (2-chlorobenzyl) -2
A mixture of -propylindole-6-carboxylic acid methyl ester (123 mg) and morpholine (1 ml) was added to 5
Stirred at 0 ° C. for 2.5 hours. After cooling to 20 ° C., the reaction mixture was extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid and water, dried over magnesium sulfate and evaporated under reduced pressure.
The residue was chromatographed on silica gel, eluting with a mixture of ethyl acetate-hexane (1: 2) to give 1- (2
-Chlorobenzyl) -3-morpholinoacetyl-2-propylindole-6-carboxylic acid methyl ester (94
mg) as a colorless amorphous. IR (KBr): 1712, 1657 cm-1 NMR (CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.60-1.65 (2H,
m), 2.70-2.75 (4H, m), 3.06 (2H, t, J = 7Hz), 3.84 (4H,
t, J = 7Hz), 3.90 (2H, s), 3.92 (3H, s), 5.52 (2H, s),
6.24 (1H, d, J = 7.5Hz), 7.06 (1H, t, J = 7.5Hz), 7.24 (1H,
t, J = 7.5Hz), 7.48 (1H, d, J = 7.5Hz), 7.94-7.98 (3H, m) MASS (m / z): 469 (M+ +1)
【０２７４】製造例103 １−（２−クロロベンジル）−３−ホルミル−２−プロ
ピルインドール−６−カルボン酸メチルエステル（263m
g）、２−メチル−２−ブテン（220mg）および燐酸二水
素ナトリウム（128mg）の第三級ブタノール（７ml）−
水（1.3ml）混合物中混合物に、20℃で、亜塩素酸ナト
リウム（219mg）を加えた。反応混合物を40℃で２時間
撹拌する。反応混合物を、０℃で、１Ｎ塩酸で酸性化
し、クロロホルムで３回抽出する。有機層を硫酸ナトリ
ウムで乾燥し、減圧下で蒸発させた。残留物をシリカゲ
ルクロマトグラフィーに付し、酢酸エチル−ヘキサン
（１：２）混合物で溶出して、１−（２−クロロベンジ
ル）−６−メトキシカルボニル−２−プロピルインドー
ル−３−カルボン酸(94mg)を淡黄色結晶として得た。 mp : 229−231℃ (分解) IR (KBr) : 1715, 1658, 1441, 1275, 1227 cm-1 NMR (CDCl3,δ) : 1.05 (3H,t,J=7Hz), 1.60-1.70 (2H,
m), 3.10-3.18 (2H,m), 3.93 (3H,s), 5.54 (2H,s), 6.
78 (1H,d,J=7.5Hz), 7.06 (1H,t,J=7.5Hz), 7.21-7.25
(1H,m), 7.49 (1H,d,J=7.5Hz), 7.95 (1H,s),7.99 (1H,
d,J=8Hz), 8.33 (1H,d,J=8Hz) MASS (m/z) : 384 (M+-1), 77 (bp)Production Example 103 1- (2-Chlorobenzyl) -3-formyl-2-propylindole-6-carboxylic acid methyl ester (263 m
g), tert-butanol (7 ml) of 2-methyl-2-butene (220 mg) and sodium dihydrogen phosphate (128 mg)
To the mixture in a mixture of water (1.3 ml) at 20 ° C. was added sodium chlorite (219 mg). The reaction mixture is stirred at 40 ° C. for 2 hours. The reaction mixture is acidified at 0 ° C. with 1N hydrochloric acid and extracted three times with chloroform. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate-hexane (1: 2) to give 1- (2-chlorobenzyl) -6-methoxycarbonyl-2-propylindole-3-carboxylic acid (94 mg). ) Was obtained as pale yellow crystals. mp: 229-231 ° C (decomposition) IR (KBr): 1715, 1658, 1441, 1275, 1227 cm-1 NMR (CDCl3 , δ): 1.05 (3H, t, J = 7Hz), 1.60-1.70 (2H ,
m), 3.10-3.18 (2H, m), 3.93 (3H, s), 5.54 (2H, s), 6.
78 (1H, d, J = 7.5Hz), 7.06 (1H, t, J = 7.5Hz), 7.21-7.25
(1H, m), 7.49 (1H, d, J = 7.5Hz), 7.95 (1H, s), 7.99 (1H,
d, J = 8Hz), 8.33 (1H, d, J = 8Hz) MASS (m / z): 384 (M + -1), 77 (bp)
【０２７５】製造例104 60％水素化ナトリウム（470mg）のＮ,Ｎ−ジメチルホル
ムアミド（６ml）懸濁液に、２−エチルインドール−６
−カルボン酸メチルエステル（1.99ｇ）のＮ,Ｎ−ジメ
チルホルムアミド（12ml）溶液を20℃で加えた。混合物
を20℃で30分間撹拌した。この混合物に、20℃で、臭化
２−クロロベンジル（2.21ｇ）を加え、混合物を20℃で
5.5時間撹拌した。Ｎ,Ｎ−ジメチルホルムアミドを蒸発
させて除去し、残留物を酢酸エチルで抽出した。有機層
を水および食塩水で洗い、硫酸ナトリウムで乾燥し、減
圧下で蒸発させた。残留物をシリカゲルクロマトグラフ
ィーに付し、酢酸エチル−ヘキサン（１：８）混合物で
溶出し、得た結晶をヘキサンで洗って、１−（２−クロ
ロベンジル）−２−エチルインドール−６−カルボン酸
メチルエステル（2.71ｇ）を無色結晶として得た。 mp : 87−89℃ IR (KBr) : 1709, 1278, 1236 cm-1 NMR (CDCl3,δ) : 1.35 (3H,t,J=7Hz), 2.67 (2H,q,J=7
Hz), 3.91 (3H,s),5.45 (2H,s), 6.17 (1H,d,J=7Hz),
6.46 (1H,s), 7.02 (1H,dd,J=7,7Hz), 7.19 (1H,dd,J=
7, 7Hz), 7.44 (1H,d,J=7Hz), 7.62 (1H,d,J=7Hz),7.72
(1H,d,J=7Hz), 7.93 (1H,s) MASS (m/z) : 328 (M++1), 76 (bp)Production Example 104 To a suspension of 60% sodium hydride (470 mg) in N, N-dimethylformamide (6 ml) was added 2-ethylindole-6.
A solution of carboxylic acid methyl ester (1.99 g) in N, N-dimethylformamide (12 ml) was added at 20 ° C. The mixture was stirred at 20 ° C. for 30 minutes. To this mixture at 20 ° C. was added 2-chlorobenzyl bromide (2.21 g) and the mixture was added at 20 ° C.
Stir for 5.5 hours. The N, N-dimethylformamide was removed by evaporation and the residue was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography, eluted with a mixture of ethyl acetate-hexane (1: 8), and the obtained crystals were washed with hexane to give 1- (2-chlorobenzyl) -2-ethylindole-6-carboxylic acid. The acid methyl ester (2.71 g) was obtained as colorless crystals. mp: 87-89 ° C IR (KBr): 1709, 1278, 1236 cm-1 NMR (CDCl3 , δ): 1.35 (3H, t, J = 7Hz), 2.67 (2H, q, J = 7
Hz), 3.91 (3H, s), 5.45 (2H, s), 6.17 (1H, d, J = 7Hz),
6.46 (1H, s), 7.02 (1H, dd, J = 7,7Hz), 7.19 (1H, dd, J =
7,7Hz), 7.44 (1H, d, J = 7Hz), 7.62 (1H, d, J = 7Hz), 7.72
(1H, d, J = 7Hz), 7.93 (1H, s) MASS (m / z): 328 (M+ +1), 76 (bp)
【０２７６】製造例105 製造例85と同様にして、次の化合物を製造した。 １−（２−クロロベンジル）−２−エチル−３−ホルミ
ルインドール−６−カルボン酸メチルエステル mp : 168−169℃ IR (KBr) : 1715, 1650 cm-1 NMR (CDCl3,δ) : 1.27 (3H,t,J=7Hz), 3.06 (2H,q,J=7
Hz), 3.90 (3H,s),5.50 (2H,s), 6.18 (1H,d,J=7Hz),
7.05 (1H,t,J=7Hz), 7.21-7.24 (1H,m), 7.48 (1H,d,J=
7.5Hz), 7.95 (1H,s), 8.01 (1H,d,J=7Hz), 8.28 (1H,
d,J=7Hz), 10.25 (1H,s) MASS (m/z) : 356 (M++1), 76 (bp)Production Example 105 The following compound was produced in the same manner as in Production Example 85. 1- (2-chlorobenzyl) -2-ethyl-3-formylindole-6-carboxylic acid methyl ester mp: 168-169 ° C IR (KBr): 1715, 1650 cm-1 NMR (CDCl3 , δ): 1.27 (3H, t, J = 7Hz), 3.06 (2H, q, J = 7
Hz), 3.90 (3H, s), 5.50 (2H, s), 6.18 (1H, d, J = 7Hz),
7.05 (1H, t, J = 7Hz), 7.21-7.24 (1H, m), 7.48 (1H, d, J =
7.5Hz), 7.95 (1H, s), 8.01 (1H, d, J = 7Hz), 8.28 (1H,
d, J = 7Hz), 10.25 (1H, s) MASS (m / z): 356 (M+ +1), 76 (bp)
【０２７７】製造例106 １−（２−クロロベンジル）−３−イソブチリル−２−
プロピルインドール−６−カルボン酸（100mg）、ジフ
ェニルリン酸アジド（97mg）およびトリエチルアミン
（53mg）の第三級ブタノール（４ml）中混合物を、２時
間還流下に加熱し、つぎに、酢酸エチルと希塩酸とに分
配した。有機層を炭酸ナトリウム水溶液で洗い、硫酸マ
グネシウムで乾燥し、減圧下で蒸発させた。残留物を、
ヘキサン−酢酸エチル（２：１）混合物を用いてのシリ
カゲル薄層クロマトグラフィーにより精製して、６−第
三級ブトキシカルボニルアミノ−１−（２−クロロベン
ジル）−３−イソブチリル−２−プロピルインドール
（125mg）を淡黄色油状物として得た。 NMR (CDCl3,δ) : 0.98 (3H,t,J=7Hz), 1.28 (6H,d,J=7
Hz), 1.48 (9H,s),1.52-1.64 (2H,m), 2.96-3.02 (2H,
m), 3.54 (1H,septet,J=7Hz), 5.42(2H,s), 6.30 (1H,
d,J=8Hz), 6.52 (1H,s), 7.05 (1H,t,J=8Hz), 7.09(1H,
d,J=8Hz), 7.20 (1H,t,J=8Hz), 7.36-7.45 (2H,m), 7.8
2 (1H,d,J=8Hz)Production Example 106 1- (2-chlorobenzyl) -3-isobutyryl-2-
A mixture of propylindole-6-carboxylic acid (100 mg), diphenylphosphoric azide (97 mg) and triethylamine (53 mg) in tert-butanol (4 ml) was heated under reflux for 2 hours, then ethyl acetate and dilute hydrochloric acid And distributed. The organic layer was washed with aqueous sodium carbonate, dried over magnesium sulfate and evaporated under reduced pressure. The residue,
Purification by silica gel thin layer chromatography using a hexane-ethyl acetate (2: 1) mixture gives 6-tert-butoxycarbonylamino-1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole. (125 mg) as a pale yellow oil. NMR (CDCl3 , δ): 0.98 (3H, t, J = 7Hz), 1.28 (6H, d, J = 7
Hz), 1.48 (9H, s), 1.52-1.64 (2H, m), 2.96-3.02 (2H,
m), 3.54 (1H, septet, J = 7Hz), 5.42 (2H, s), 6.30 (1H,
d, J = 8Hz), 6.52 (1H, s), 7.05 (1H, t, J = 8Hz), 7.09 (1H, s
d, J = 8Hz), 7.20 (1H, t, J = 8Hz), 7.36-7.45 (2H, m), 7.8
2 (1H, d, J = 8Hz)
【０２７８】製造例107 ６−第三級ブトキシカルボニルアミノ−１−（２−クロ
ロベンジル）−３−イソブチリル−２−プロピルインド
ール（110mg）の酢酸エチル（１ml）溶液に、20℃で、
４Ｎ塩化水素−酢酸エチル溶液を加え、混合物を同温度
で４時間撹拌した。沈殿を濾取し、酢酸エチルで洗っ
て、６−アミノ−１−（２−クロロベンジル）−３−イ
ソブチリル−２−プロピルインドール塩酸塩（50mg）を
粉末として得た。 NMR (DMSO-d6,δ) : 0.92 (3H,t,J=7Hz), 1.18 (6H,d,J
=7Hz), 1.49 (2H,sextet,J=7Hz), 3.02-3.08 (2H,m),
3.52 (1H,septet,J=7Hz), 5.58(2H,s), 6.24 (1H,d,J=8
Hz), 7.17-7.35 (4H,m), 7.57 (1H,d,J=8Hz),8.02 (1H,
d,J=8Hz)Production Example 107 A solution of 6-tert-butoxycarbonylamino-1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole (110 mg) in ethyl acetate (1 ml) was added at 20 ° C.
A 4N hydrogen chloride-ethyl acetate solution was added, and the mixture was stirred at the same temperature for 4 hours. The precipitate was collected by filtration and washed with ethyl acetate to give 6-amino-1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole hydrochloride (50 mg) as a powder. NMR (DMSO-d6 , δ): 0.92 (3H, t, J = 7Hz), 1.18 (6H, d, J
= 7Hz), 1.49 (2H, sextet, J = 7Hz), 3.02-3.08 (2H, m),
3.52 (1H, septet, J = 7Hz), 5.58 (2H, s), 6.24 (1H, d, J = 8
Hz), 7.17-7.35 (4H, m), 7.57 (1H, d, J = 8Hz), 8.02 (1H,
d, J = 8Hz)
【０２７９】製造例108 ６−第三級ブトキシカルボニルアミノ−１−（２−クロ
ロベンジル）−３−イソブチリル−２−プロピルインド
ール（581mg）の酢酸エチル（５ml）溶液に、20℃で、
４Ｎ塩化水素−酢酸エチル溶液（５ml）を加えた。反応
混合物を20℃で6.5時間撹拌し、つぎに、１Ｎ水酸化ナ
トリウム水溶液で希釈、抽出した。有機層を硫酸マグネ
シウムで乾燥し、減圧下で蒸発させた。残留物をシリカ
ゲルクロマトグラフィーに付し、酢酸エチル−ヘキサン
（１：６→１：４）混合物で溶出して、６−アミノ−１
−（２−クロロベンジル）−３−イソブチリル−２−プ
ロピルインドール（361mg）を黄色油状物として得た。 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.51-1.64 (2H,m), 2.98-3.03 (2H,m), 3.49-3.57
(1H,m), 5.34 (2H,s), 6.36 (1H,d,J=7.5Hz), 6.46 (1
H,s), 6.71 (1H,d,J=7.5Hz), 7.08 (1H,t,J=7.5Hz),7.2
1 (1H,t,J=7.5Hz), 7.45 (1H,d,J=7.5Hz), 7.85 (1H,d,
J=7.5Hz) MASS (m/z) : 369 (M++1)Production Example 108 A solution of 6-tert-butoxycarbonylamino-1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole (581 mg) in ethyl acetate (5 ml) was added at 20 ° C.
A 4N hydrogen chloride-ethyl acetate solution (5 ml) was added. The reaction mixture was stirred at 20 ° C. for 6.5 hours, then diluted and extracted with a 1N aqueous sodium hydroxide solution. The organic layer was dried over magnesium sulfate and evaporated under reduced pressure. The residue was chromatographed on silica gel, eluting with a mixture of ethyl acetate-hexane (1: 6 → 1: 4) to give 6-amino-1.
-(2-Chlorobenzyl) -3-isobutyryl-2-propylindole (361 mg) was obtained as a yellow oil. NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.29 (6H, d, J = 7
Hz), 1.51-1.64 (2H, m), 2.98-3.03 (2H, m), 3.49-3.57
(1H, m), 5.34 (2H, s), 6.36 (1H, d, J = 7.5Hz), 6.46 (1
H, s), 6.71 (1H, d, J = 7.5Hz), 7.08 (1H, t, J = 7.5Hz), 7.2
1 (1H, t, J = 7.5Hz), 7.45 (1H, d, J = 7.5Hz), 7.85 (1H, d,
J = 7.5Hz) MASS (m / z): 369 (M+ +1)
【０２８０】製造例109 ６−アミノ−１−（２−クロロベンジル）−３−イソブ
チリル−２−プロピルインドール（79mg）とトリエチル
アミン（0.065ml）とのジクロロメタン（２ml）溶液
に、０℃で撹拌下、塩化アセチル（0.02ml）を加えた。
反応混合物を20℃で２時間撹拌し、つぎにジクロロメタ
ンで希釈した。有機層を１Ｎ塩酸、水、炭酸ナトリウム
水溶液、水および食塩水で洗い、硫酸マグネシウムで乾
燥し、減圧下で蒸発させた。残留物をシリカゲルクロマ
トグラフィーに付し、酢酸エチル−ヘキサン（２：３）
混合物で溶出し、得られた結晶を酢酸エチル−ヘキサン
混合物から再結晶して、６−アセトアミド−１−（２−
クロロベンジル）−３−イソブチリル−２−プロピルイ
ンドール（48mg）を無色結晶として得た。 mp : 147−148℃ IR (KBr) : 1664, 1648, 1507, 1412 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.51-1.65 (2H,m), 2.17 (3H,s), 2.99-3.05 (2H,
m), 3.49-3.58 (1H,m), 5.43 (2H,s),6.30 (1H,d,J=7.5
Hz), 7.04 (1H,t,J=7.5Hz), 7.13-7.23 (3H,m), 7.44(1
H,d,J=7.5Hz), 7.72 (1H,s), 7.85 (1H,d,J=7.5Hz) MASS (m/z) : 411 (M++1)Production Example 109 A solution of 6-amino-1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole (79 mg) and triethylamine (0.065 ml) in dichloromethane (2 ml) was stirred at 0 ° C. , Acetyl chloride (0.02 ml) was added.
The reaction mixture was stirred at 20 ° C. for 2 hours and then diluted with dichloromethane. The organic layer was washed with 1N hydrochloric acid, water, aqueous sodium carbonate solution, water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography, and ethyl acetate-hexane (2: 3).
The mixture was eluted and the resulting crystals were recrystallized from an ethyl acetate-hexane mixture to give 6-acetamido-1- (2-
(Chlorobenzyl) -3-isobutyryl-2-propylindole (48 mg) was obtained as colorless crystals. mp: 147-148 ° C IR (KBr): 1664, 1648, 1507, 1412 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.29 (6H, d, J = 7
Hz), 1.51-1.65 (2H, m), 2.17 (3H, s), 2.99-3.05 (2H,
m), 3.49-3.58 (1H, m), 5.43 (2H, s), 6.30 (1H, d, J = 7.5
Hz), 7.04 (1H, t, J = 7.5Hz), 7.13-7.23 (3H, m), 7.44 (1
H, d, J = 7.5Hz), 7.72 (1H, s), 7.85 (1H, d, J = 7.5Hz) MASS (m / z): 411 (M+ +1)
【０２８１】製造例110 ６−アミノ−１−（２−クロロベンジル）−３−イソブ
チリル−２−プロピルインドール（100mg）のクロロホ
ルム（２ml）溶液に、０℃で撹拌下、メチルイソシアナ
ート（0.5ml）を加えた。反応混合物を20℃で１時間撹
拌し、つぎに蒸発させた。残留物をシリカゲルクロマト
グラフィーに付し、酢酸エチル−ヘキサン（１：１）混
合物で溶出し、得られた結晶を酢酸エチル−ヘキサン混
合物から再結晶して、１−（２−クロロベンジル）−３
−イソブチリル−６−（３−メチルウレイド）−２−プ
ロピルインドール（75mg）を無色結晶として得た。 mp : 106−108.5℃ IR (KBr) : 1635, 1550, 1506 cm-1 NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.53-1.65 (2H,m), 2.78 (3H,d,J=7Hz), 3.00-3.0
6 (2H,m), 3.49-3.57 (1H,m), 4.61(1H,d,J=7Hz), 5.42
(2H,s), 6.29-6.32 (2H,m), 7.02-7.07 (2H,m),7.22
(1H,ddd,J=7.5, 7.5, 1Hz), 7.46 (1H,d,J=7.5Hz), 7.8
8 (1H,d,J=7.5Hz) MASS (m/z) : 426 (M++1), 76 (bp)Production Example 110 A solution of 6-amino-1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole (100 mg) in chloroform (2 ml) was stirred at 0 ° C. with methyl isocyanate (0.5 ml). ) Was added. The reaction mixture was stirred at 20 ° C. for 1 hour and then evaporated. The residue was subjected to silica gel chromatography, eluted with an ethyl acetate-hexane (1: 1) mixture, and the obtained crystals were recrystallized from an ethyl acetate-hexane mixture to give 1- (2-chlorobenzyl) -3.
-Isobutyryl-6- (3-methylureido) -2-propylindole (75 mg) was obtained as colorless crystals. mp: 106-108.5 ° C IR (KBr): 1635, 1550, 1506 cm-1 NMR (CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.53-1.65 (2H, m), 2.78 (3H, d, J = 7Hz), 3.00-3.0
6 (2H, m), 3.49-3.57 (1H, m), 4.61 (1H, d, J = 7Hz), 5.42
(2H, s), 6.29-6.32 (2H, m), 7.02-7.07 (2H, m), 7.22
(1H, ddd, J = 7.5, 7.5, 1Hz), 7.46 (1H, d, J = 7.5Hz), 7.8
8 (1H, d, J = 7.5Hz) MASS (m / z): 426 (M+ +1), 76 (bp)
【０２８２】製造例111 ６−アミノ−１−（２−クロロベンジル）−３−イソブ
チリル−２−プロピルインドール（147mg）のジクロロ
メタン（２ml）溶液に、０℃で撹拌下、酢酸蟻酸混合酸
無水物（0.5ml）を加えた。反応混合物を０℃で10分間
撹拌し、つぎにジクロロメタンで希釈した。有機層を水
および食塩水で洗い、硫酸マグネシウムで乾燥し、減圧
下で蒸発させた。残留物をシリカゲルクロマトグラフィ
ーに付し、酢酸エチル−ヘキサン（１：２）混合物で溶
出し、得られた結晶を酢酸エチル−ヘキサン混合物から
再結晶して、１−（２−クロロベンジル）−６−ホルム
アミド−３−イソブチリル−２−プロピルインドール
（85mg）を無色結晶として得た。 mp : 113−115℃ IR (KBr) : 1666, 1647, 1508 cm-1 NMR (CDCl3,δ) : 1.00, 1.03 (3H,t and t,J=7Hz), 1.
28, 1.30 (6H,d andd,J=7Hz), 1.54-1.65 (2H,m), 2.99
-3.09 (2H,m), 3.47-3.57 (1H,m),5.43 (2H,d,J=4Hz),
6.31 (1H,d,J=7.5Hz), 6.82-7.10 (2H,m), 7.17-7.25
(2H,m), 7.43-7.77 (2H,m), 7.90 (1H,dd,J=10, 7.5H
z), 8.37-8.58(1H,m) MASS (m/z) : 397 (M++1)Production Example 111 A mixed acid anhydride of formic acetate and formic acid was stirred at 0 ° C. in a solution of 6-amino-1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole (147 mg) in dichloromethane (2 ml) at 0 ° C. (0.5 ml) was added. The reaction mixture was stirred at 0 ° C. for 10 minutes and then diluted with dichloromethane. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography, eluted with a mixture of ethyl acetate-hexane (1: 2), and the obtained crystals were recrystallized from a mixture of ethyl acetate-hexane to give 1- (2-chlorobenzyl) -6. -Formamide-3-isobutyryl-2-propylindole (85 mg) was obtained as colorless crystals. mp: 113-115 ° C IR (KBr): 1666, 1647, 1508 cm-1 NMR (CDCl3 , δ): 1.00, 1.03 (3H, t and t, J = 7Hz), 1.
28, 1.30 (6H, d andd, J = 7Hz), 1.54-1.65 (2H, m), 2.99
-3.09 (2H, m), 3.47-3.57 (1H, m), 5.43 (2H, d, J = 4Hz),
6.31 (1H, d, J = 7.5Hz), 6.82-7.10 (2H, m), 7.17-7.25
(2H, m), 7.43-7.77 (2H, m), 7.90 (1H, dd, J = 10, 7.5H
z), 8.37-8.58 (1H, m) MASS (m / z): 397 (M+ +1)
【０２８３】製造例112 ３−イソブチリル−１−（２−ニトロベンジル）−２−
プロピルインドール−６−カルボキサミド（316mg）の
メタノール（10ml）溶液を、10％パラジウム炭素の存在
下、20℃で６時間水素化処理した。触媒を濾別し、濾液
を減圧下で蒸発させた。残留物をシリカゲルクロマトグ
ラフィーに付し、メタノール−クロロホルム（１：30）
混合物で溶出し、得られた油状物をクロロホルム（10m
l）−メタノール（20ml）混合物に溶解させた。この溶
液に、10％塩化水素−メタノール溶液（0.9ml）を加
え、混合物を20℃で１時間撹拌し、減圧下で蒸発させ
た。残留物をメタノール−ジイソプロピルエーテルから
再結晶して、１−（２−アミノベンジル）−３−イソブ
チリル−２−プロピルインドール−６−カルボキサミド
塩酸塩（415mg）を無色結晶として得た。 mp : 255−257℃ IR (KBr) : 1650, 1550, 1455 cm-1 NMR (DMSO-d6,δ) : 0.95 (3H,t,J=7Hz), 1.20 (3H,t,J
=7Hz), 1.46-1.59(2H,m), 2.96-3.01 (2H,m), 5.67 (2
H,s), 5.89 (1H,d,J=7.5Hz), 6.87(1H,br t,J=7Hz), 7.
19-7.34 (3H,m), 7.80 (1H,d,J=7.5Hz), 7.92-7.98(2H,
m), 8.03 (1H,s) MASS (m/z) : 378 (M++1), 86 (bp)Production Example 112 3-Isobutyryl-1- (2-nitrobenzyl) -2-
A solution of propylindole-6-carboxamide (316 mg) in methanol (10 ml) was hydrogenated at 20 ° C. for 6 hours in the presence of 10% palladium on carbon. The catalyst was filtered off and the filtrate was evaporated under reduced pressure. The residue was subjected to silica gel chromatography, and methanol-chloroform (1:30)
The mixture was eluted, and the resulting oil was purified with chloroform (10 m
l)-Dissolved in a mixture of methanol (20 ml). To this solution was added a 10% hydrogen chloride-methanol solution (0.9 ml), the mixture was stirred at 20 ° C. for 1 hour and evaporated under reduced pressure. The residue was recrystallized from methanol-diisopropyl ether to give 1- (2-aminobenzyl) -3-isobutyryl-2-propylindole-6-carboxamide hydrochloride (415 mg) as colorless crystals. mp: 255-257 ° C IR (KBr): 1650, 1550, 1455 cm-1 NMR (DMSO-d6 , δ): 0.95 (3H, t, J = 7Hz), 1.20 (3H, t, J
= 7Hz), 1.46-1.59 (2H, m), 2.96-3.01 (2H, m), 5.67 (2
H, s), 5.89 (1H, d, J = 7.5Hz), 6.87 (1H, brt, J = 7Hz), 7.
19-7.34 (3H, m), 7.80 (1H, d, J = 7.5Hz), 7.92-7.98 (2H,
m), 8.03 (1H, s) MASS (m / z): 378 (M+ +1), 86 (bp)
【０２８４】製造例113 １−（２−クロロベンジル）−３−メトキシアセチル−
２−プロピルインドール−６−カルボキサミド（168m
g）のジクロロメタン（10ml）−メタノール（0.5ml）混
合物溶液に、-53℃で、１Ｍ三臭化硼素−ジクロロメタ
ン溶液（2.5ml）を加えた。反応混合物を３時間かけ
て、-12℃まで徐々に昇温させた。つぎに、１Ｍ三臭化
硼素ジクロロメタン溶液（2.5ml）を加え、混合物を-12
℃で20分間撹拌した。反応混合物を水で希釈し、10％メ
タノールクロロホルム溶液で抽出した。有機層を炭酸ナ
トリウム水溶液、水および食塩水で洗い、硫酸マグネシ
ウムで乾燥し、減圧下で蒸発させた。残留物を酢酸エチ
ルから結晶化し、ヘキサンで洗って、１−（２−クロロ
ベンジル）−３−ヒドロキシアセチル−２−プロピルイ
ンドール−６−カルボキサミド（120mg）を無色結晶と
して得た。 mp : 231−233.5℃ IR (KBr) : 3405, 3159, 1673, 1647, 1616, 1395 cm-1 NMR (DMSO-d6,δ) : 0.94 (3H,t,J=7Hz), 1.40-1.52 (2
H,m), 3.05 (3H,t,J=7Hz), 4.75 (2H,t,J=6Hz), 4.90
(1H,t,J=6Hz), 5.65 (2H,s), 6.22(1H,d,J=7.5Hz), 7.1
8 (1H,t,J=7.5Hz), 7.27-7.35 (2H,m), 7.58 (1H,d,J=
7.5Hz), 7.81 (1H,d,J=7.5Hz), 7.92 (2H,d,J=7.5Hz),
8.01 (1H,s) MASS (m/z) : 385 (M++1), 86 (bp)Production Example 113 1- (2-chlorobenzyl) -3-methoxyacetyl-
2-propylindole-6-carboxamide (168m
To a mixed solution of g) in dichloromethane (10 ml) -methanol (0.5 ml) at -53 ° C was added a 1 M boron tribromide-dichloromethane solution (2.5 ml). The reaction mixture was gradually warmed to -12 ° C over 3 hours. Next, a 1 M boron tribromide dichloromethane solution (2.5 ml) was added, and the mixture was added to -12 ml.
Stirred at C for 20 minutes. The reaction mixture was diluted with water and extracted with a 10% methanol-chloroform solution. The organic layer was washed with aqueous sodium carbonate, water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was crystallized from ethyl acetate and washed with hexane to give 1- (2-chlorobenzyl) -3-hydroxyacetyl-2-propylindole-6-carboxamide (120 mg) as colorless crystals. mp: 231-233.5 ° C IR (KBr): 3405, 3159, 1673, 1647, 1616, 1395 cm-1 NMR (DMSO-d6 , δ): 0.94 (3H, t, J = 7Hz), 1.40-1.52 ( Two
H, m), 3.05 (3H, t, J = 7Hz), 4.75 (2H, t, J = 6Hz), 4.90
(1H, t, J = 6Hz), 5.65 (2H, s), 6.22 (1H, d, J = 7.5Hz), 7.1
8 (1H, t, J = 7.5Hz), 7.27-7.35 (2H, m), 7.58 (1H, d, J =
7.5Hz), 7.81 (1H, d, J = 7.5Hz), 7.92 (2H, d, J = 7.5Hz),
8.01 (1H, s) MASS (m / z): 385 (M+ +1), 86 (bp)
【０２８５】製造例114 ３−イソブチリル−２−プロピルインドール−６−カル
ボン酸ベンジルエステル（207mg）とジイソプロピルエ
チルアミン（295mg）とのジクロロメタン（６ml）中混
合物に、０℃で撹拌下、塩化２−クロロベンゾイル（29
9mg）および４−ジメチルアミノピリジン（12mg）を加
えた。反応混合物を15時間還流下に加熱した。反応混合
物を20℃まで冷却し、１Ｎ塩酸、水、飽和炭酸ナトリウ
ム、水および食塩水で洗った。有機層を硫酸ナトリウム
で乾燥し、減圧下で蒸発させた。残留物をシリカゲルク
ロマトグラフィーに付し、酢酸エチル−ヘキサン（１：
10）混合物で溶出して、１−（２−クロロベンゾイル）
−３−イソブチリル−２−プロピルインドール−６−カ
ルボン酸ベンジルエステル（330mg）を黄色結晶として
得た。 mp : 67.5−70℃ IR (KBr) : 1780, 1710, 1700, 1300 cm-1 NMR (CDCl3,δ) : 0.99 (3H,t,J=7Hz), 1.27 (6H,t,J=7
Hz), 1.74 (2H,sextet,J=7Hz), 3.12 (2H,t,J=7Hz), 3.
39-3.48 (1H,m), 5.25 (2H,s),7.33-7.45 (8H,m), 7.53
-7.58 (2H,m), 7.80 (1H,d,J=7.5Hz), 7.98-8.05 (1H,
m) MASS (m/z) : 502 (M++1)Preparation 114 A mixture of 3-isobutyryl-2-propylindole-6-carboxylic acid benzyl ester (207 mg) and diisopropylethylamine (295 mg) in dichloromethane (6 ml) was stirred at 0 ° C. under stirring for 2-chloro chloride. Benzoyl (29
9 mg) and 4-dimethylaminopyridine (12 mg) were added. The reaction mixture was heated under reflux for 15 hours. The reaction mixture was cooled to 20 ° C. and washed with 1N hydrochloric acid, water, saturated sodium carbonate, water and brine. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography, and ethyl acetate-hexane (1: 1).
10) Eluting with the mixture, 1- (2-chlorobenzoyl)
-3-Isobutyryl-2-propylindole-6-carboxylic acid benzyl ester (330 mg) was obtained as yellow crystals. mp: 67.5-70 ° C IR (KBr): 1780, 1710, 1700, 1300 cm-1 NMR (CDCl3 , δ): 0.99 (3H, t, J = 7Hz), 1.27 (6H, t, J = 7
Hz), 1.74 (2H, sextet, J = 7Hz), 3.12 (2H, t, J = 7Hz), 3.
39-3.48 (1H, m), 5.25 (2H, s), 7.33-7.45 (8H, m), 7.53
-7.58 (2H, m), 7.80 (1H, d, J = 7.5Hz), 7.98-8.05 (1H,
m) MASS (m / z): 502 (M+ +1)
【０２８６】製造例114 １−（２−クロロベンゾイル）−３−イソブチリル−２
−プロピルインドール−６−カルボン酸ベンジルエステ
ル（304mg）のメタノール（６ml）溶液を、10％パラジ
ウム炭素の存在下、20℃で９時間水素化処理した。触媒
を濾別し、濾液を減圧下で蒸発させた。残留物をシリカ
ゲルクロマトグラフィーに付し、メタノール−クロロホ
ルム（１：30）混合物で溶出し、得られた結晶を酢酸エ
チル−ヘキサン混合物から再結晶して、１−（２−クロ
ロベンゾイル）−３−イソブチリル−２−プロピルイン
ドール−６−カルボン酸（189mg）を無色結晶として得
た。 IR (KBr) : 1710, 1695, 1980, 1315 cm-1 NMR (CDCl3,δ) : 0.95 (3H,t,J=7Hz), 1.27 (6H,t,J=7
Hz), 1.64-1.75 (2H,m), 3.03-3.09 (1H,m), 3.40-3.49
(1H,m), 7.48-7.52 (2H,m), 7.58-7.67 (3H,m), 7.92
(2H,AB,J=8, 7.5Hz)Production Example 114 1- (2-chlorobenzoyl) -3-isobutyryl-2
A solution of -propylindole-6-carboxylic acid benzyl ester (304 mg) in methanol (6 ml) was hydrogenated at 20 ° C for 9 hours in the presence of 10% palladium on carbon. The catalyst was filtered off and the filtrate was evaporated under reduced pressure. The residue was subjected to silica gel chromatography, eluted with a mixture of methanol and chloroform (1:30), and the obtained crystals were recrystallized from a mixture of ethyl acetate and hexane to give 1- (2-chlorobenzoyl) -3-. Isobutyryl-2-propylindole-6-carboxylic acid (189 mg) was obtained as colorless crystals. IR (KBr): 1710, 1695, 1980, 1315 cm-1 NMR (CDCl3 , δ): 0.95 (3H, t, J = 7Hz), 1.27 (6H, t, J = 7
Hz), 1.64-1.75 (2H, m), 3.03-3.09 (1H, m), 3.40-3.49
(1H, m), 7.48-7.52 (2H, m), 7.58-7.67 (3H, m), 7.92
(2H, AB, J = 8,7.5Hz)
【０２８７】製造例116 １−（２−クロロベンジル）−３−ホルミルインドール
−６−カルボキサミド（47mg）のジメチルホルムアミド
（1.6ml）溶液に、撹拌下、無水クロム酸（125mg）およ
び硫酸（0.05ml）を加え、混合物を20℃で５間時間撹拌
した。生じた混合物を減圧下で蒸発させ、残留物をシリ
カゲルクロマトグラフィーに付し、クロロホルム−メタ
ノール（９：１）混合物で溶出して、６−カルバモイル
−１−（２−クロロベンジル）インドール−３−カルボ
ン酸（8.3mg）を固体として得た。 mp : 240℃ (分解) NMR (DMSO-d6,δ) : 5.64 (2H,s), 6.71 (1H,d,J=8Hz),
7.26 (1H,t,J=8Hz),7.28 (1H,br s), 7.36 (1H,t,J=8H
z), 7.56 (1H,d,J=8Hz), 7.78 (1H,d,J=8Hz), 7.92 (1
H,br s), 8.06 (1H,s), 8.07 (1H,d,J=8Hz), 8.20(1H,
s)Production Example 116 Chromic anhydride (125 mg) and sulfuric acid (0.05 ml) were added to a solution of 1- (2-chlorobenzyl) -3-formylindole-6-carboxamide (47 mg) in dimethylformamide (1.6 ml) with stirring. ) Was added and the mixture was stirred at 20 ° C. for 5 hours. The resulting mixture was evaporated under reduced pressure and the residue was chromatographed on silica gel, eluting with a chloroform-methanol (9: 1) mixture to give 6-carbamoyl-1- (2-chlorobenzyl) indole-3-. The carboxylic acid (8.3 mg) was obtained as a solid. mp: 240 ° C (decomposition) NMR (DMSO-d6 , δ): 5.64 (2H, s), 6.71 (1H, d, J = 8Hz),
7.26 (1H, t, J = 8Hz), 7.28 (1H, br s), 7.36 (1H, t, J = 8H
z), 7.56 (1H, d, J = 8Hz), 7.78 (1H, d, J = 8Hz), 7.92 (1
H, br s), 8.06 (1H, s), 8.07 (1H, d, J = 8Hz), 8.20 (1H,
s)
【０２８８】製造例117 １−（２−クロロベンジル）−２−（１−ヒドロキシプ
ロピル）−３−イソブチリルインドール−６−カルボキ
サミド（19mg）のアセトン（３ml）溶液に、ジョーンズ
試薬を、赤色が定常的に存続するようになるまで加え
た。２−プロパノールにより反応を停止させ、つぎに混
合物を酢酸エチルで希釈し、炭酸ナトリウム水溶液およ
び食塩水で洗った。有機層を硫酸ナトリウムで乾燥し、
減圧下で蒸発させた。残留物をジイソプロピルエーテル
を用いて粉末化して、１−（２−クロロベンジル）−３
−イソブチリル−２−プロピオニルインドール−６−カ
ルボキサミド（9.3mg）を得た。 mp : 145−147℃ NMR (CDCl3,δ) : 1.15 (3H,t,J=7Hz), 1.33 (6H,d,J=7
Hz), 2.60 (2H,q,J=7Hz), 3.47 (1H,m), 5.46 (2H,s),
6.50 (1H,d,J=8Hz), 7.09 (1H,t,J=8Hz), 7.21 (1H,t,J
=8Hz), 7.42 (1H,d,J=8Hz), 7.70 (1H,d,J=8Hz),7.88
(1H,s), 7.98 (1H,s)Production Example 117 To a solution of 1- (2-chlorobenzyl) -2- (1-hydroxypropyl) -3-isobutyrylindole-6-carboxamide (19 mg) in acetone (3 ml) was added the Jones reagent in red. Was added until it remained constant. The reaction was quenched with 2-propanol, then the mixture was diluted with ethyl acetate and washed with aqueous sodium carbonate and brine. The organic layer is dried over sodium sulfate,
Evaporated under reduced pressure. The residue was triturated with diisopropyl ether to give 1- (2-chlorobenzyl) -3.
-Isobutyryl-2-propionylindole-6-carboxamide (9.3 mg) was obtained. mp: 145-147 ° C NMR (CDCl3 , δ): 1.15 (3H, t, J = 7Hz), 1.33 (6H, d, J = 7
Hz), 2.60 (2H, q, J = 7Hz), 3.47 (1H, m), 5.46 (2H, s),
6.50 (1H, d, J = 8Hz), 7.09 (1H, t, J = 8Hz), 7.21 (1H, t, J
= 8Hz), 7.42 (1H, d, J = 8Hz), 7.70 (1H, d, J = 8Hz), 7.88
(1H, s), 7.98 (1H, s)
【０２８９】製造例118 製造例45と同様にして、次の化合物を製造した。 ３−クロロ−１−（２−クロロベンジル）−２−プロピ
ルインドール−６−カルボキサミド mp : 163−166℃ NMR (CDCl3,δ) : 0.95 (3H,t,J=7Hz), 1.58 (2H,m),
2.73 (2H,t,J=7Hz),5.43 (2H,s), 6.19 (1H,d,J=8Hz),
7.01 (1H,t,J=8Hz), 7.18 (1H,t,J=8Hz), 7.43 (1H,d,J
=8Hz), 7.54 (1H,d,J=8Hz), 7.67 (1H,d,J=8Hz),7.82
(1H,s)Production Example 118 The following compound was produced in the same manner as in Production Example 45. 3-chloro-1- (2-chlorobenzyl) -2-propylindole-6-carboxamide mp: 163-166 ° C NMR (CDCl3 , δ): 0.95 (3H, t, J = 7Hz), 1.58 (2H, m),
2.73 (2H, t, J = 7Hz), 5.43 (2H, s), 6.19 (1H, d, J = 8Hz),
7.01 (1H, t, J = 8Hz), 7.18 (1H, t, J = 8Hz), 7.43 (1H, d, J
= 8Hz), 7.54 (1H, d, J = 8Hz), 7.67 (1H, d, J = 8Hz), 7.82
(1H, s)
【０２９０】製造例119 １−（２−ブロモベンジル）−２−プロピルインドール
−６−カルボキサミド（52mg）のジクロロメタン（３m
l）−ピリジン（１ml）混合物溶液に、撹拌下、臭化ピ
リジニウムペルブロミド（50mg）を加え、混合物を０℃
で1.5時間撹拌した。生じた混合物を酢酸エチルで希釈
し、希塩酸、炭酸ナトリウム水溶液および食塩水で洗
い、つぎに硫酸ナトリウムで乾燥し、減圧下で蒸発させ
た。残留物をヘキサン−ジイソプロピルエーテル混合物
を用いて粉末化して、３−ブロモ−１−（２−ブロモベ
ンジル）−２−プロピルインドール−６−カルボキサミ
ド（33mg）を固体として得た。 mp : 122−125℃ NMR (CDCl3,δ) : 0.98 (3H,t,J=7Hz), 1.57 (2H,m),
2.73 (2H,t,J=7Hz),5.42 (2H,s), 6.15 (1H,d,J=8Hz),
7.0-7.16 (2H,m), 7.5-7.65 (3H,m),7.79 (1H,s)Production Example 119 1- (2-Bromobenzyl) -2-propylindole-6-carboxamide (52 mg) in dichloromethane (3 m
l) To a solution of a mixture of -pyridine (1 ml) was added pyridinium bromide perbromide (50 mg) with stirring, and the mixture was cooled to 0 ° C.
For 1.5 hours. The resulting mixture was diluted with ethyl acetate, washed with dilute hydrochloric acid, aqueous sodium carbonate and brine, then dried over sodium sulfate and evaporated under reduced pressure. The residue was triturated with a hexane-diisopropyl ether mixture to give 3-bromo-1- (2-bromobenzyl) -2-propylindole-6-carboxamide (33 mg) as a solid. mp: 122-125 ° C NMR (CDCl3 , δ): 0.98 (3H, t, J = 7Hz), 1.57 (2H, m),
2.73 (2H, t, J = 7Hz), 5.42 (2H, s), 6.15 (1H, d, J = 8Hz),
7.0-7.16 (2H, m), 7.5-7.65 (3H, m), 7.79 (1H, s)
【０２９１】製造例120 製造例42と同様にして、下記(1)〜(2)に記載の化合物を
製造した。 (1) １−（２−クロロベンジル）−３−イソブチリル−
２−プロピルインドール−６−カルボニトリル mp : 130−131℃ NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.56-1.68 (2H,m), 3.06-3.12 (2H,m), 3.51 (1H,
septet,J=7Hz), 5.46 (2H,s), 6.23(1H,d,J=8Hz), 7.08
(1H,t,J=8Hz), 7.27 (1H,t,J=8Hz), 7.46-7.52(3H,m),
8.01 (1H,d,J=8Hz) (2) ９−（２−クロロベンジル）−８−オキソ−５,６,
７,８−テトラヒドロカルバゾール−２−カルボニトリ
ル mp : 173−176℃ NMR (CDCl3,δ) : 2.29 (2H,m), 2.69 (2H,t,J=7Hz),
3.08 (2H,t,J=7Hz),5.94 (2H,s), 6.30 (1H,d,J=8Hz),
7.02 (1H,t,J=8Hz), 7.19 (1H,t,J=8Hz), 7.38 (1H,d,J
=8Hz), 7.42 (1H,d,J=8Hz), 7.54 (1H,s), 7.78(1H,d,J
=8Hz)Production Example 120 The following compounds (1) and (2) were produced in the same manner as in Production Example 42. (1) 1- (2-chlorobenzyl) -3-isobutyryl-
2-propylindole-6-carbonitrile mp: 130-131 ° C NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.56-1.68 (2H, m), 3.06-3.12 (2H, m), 3.51 (1H,
(septet, J = 7Hz), 5.46 (2H, s), 6.23 (1H, d, J = 8Hz), 7.08
(1H, t, J = 8Hz), 7.27 (1H, t, J = 8Hz), 7.46-7.52 (3H, m),
8.01 (1H, d, J = 8Hz) (2) 9- (2-chlorobenzyl) -8-oxo-5,6,
7,8-tetrahydrocarbazole-2-carbonitrile mp: 173-176 ° C NMR (CDCl3 , δ): 2.29 (2H, m), 2.69 (2H, t, J = 7Hz),
3.08 (2H, t, J = 7Hz), 5.94 (2H, s), 6.30 (1H, d, J = 8Hz),
7.02 (1H, t, J = 8Hz), 7.19 (1H, t, J = 8Hz), 7.38 (1H, d, J
= 8Hz), 7.42 (1H, d, J = 8Hz), 7.54 (1H, s), 7.78 (1H, d, J
= 8Hz)
【０２９２】製造例121 １−（２−クロロベンジル）−３−イソブチリル−２−
プロピルインドール−６−カルボニトリル（70mg）のメ
タノール（２ml）−テトラヒドロフラン（２ml）混合物
溶液に、25℃で、水素化硼素ナトリウム（21mg）を加え
た。25℃で２時間撹拌後、反応混合物を酢酸エチルと１
Ｎ塩酸とに分配した。有機層を水および食塩水で洗い、
硫酸マグネシウムで乾燥し、減圧下で蒸発させた。残留
物をジイソプロピルエーテルから結晶化して、１−（２
−クロロベンジル）−３−（１−ヒドロキシ−２−メチ
ルプロピル）−２−プロピルインドール−６−カルボニ
トリル（28mg）を淡黄色結晶として得た。 mp : 126−127℃ NMR (CDCl3,δ) : 0.76 (3H,d,J=7Hz), 0.98 (3H,t,J=7
Hz), 1.22 (3H,d,J=7Hz), 1.50-1.64 (2H,m), 1.87 (1
H,d,J=2Hz), 2.32-2.44 (2H,m),2.63-2.80 (2H,m), 4.5
8 (1H,dd,J=2, 8Hz), 5.38 (2H,s), 6.15 (1H,d,J=8H
z), 7.05 (1H,t,J=8Hz), 7.22 (1H,t,J=8Hz), 7.32 (1
H,d,J=8Hz),7.38 (1H,s), 7.46 (1H,d,J=8Hz), 7.91 (1
H,d,J=8Hz)Production Example 121 1- (2-chlorobenzyl) -3-isobutyryl-2-
To a solution of propylindole-6-carbonitrile (70 mg) in a mixture of methanol (2 ml) -tetrahydrofuran (2 ml) at 25 ° C. was added sodium borohydride (21 mg). After stirring at 25 ° C. for 2 hours, the reaction mixture was mixed with ethyl acetate for 1 hour.
Partitioned with N hydrochloric acid. Wash the organic layer with water and saline,
Dry over magnesium sulfate and evaporate under reduced pressure. The residue was crystallized from diisopropyl ether to give 1- (2
-Chlorobenzyl) -3- (1-hydroxy-2-methylpropyl) -2-propylindole-6-carbonitrile (28 mg) was obtained as pale yellow crystals. mp: 126-127 ° C NMR (CDCl3 , δ): 0.76 (3H, d, J = 7Hz), 0.98 (3H, t, J = 7
Hz), 1.22 (3H, d, J = 7Hz), 1.50-1.64 (2H, m), 1.87 (1
(H, d, J = 2Hz), 2.32-2.44 (2H, m), 2.63-2.80 (2H, m), 4.5
8 (1H, dd, J = 2,8Hz), 5.38 (2H, s), 6.15 (1H, d, J = 8H
z), 7.05 (1H, t, J = 8Hz), 7.22 (1H, t, J = 8Hz), 7.32 (1
H, d, J = 8Hz), 7.38 (1H, s), 7.46 (1H, d, J = 8Hz), 7.91 (1
(H, d, J = 8Hz)
【０２９３】製造例122 製造例121と同様にして、次の化合物を製造した。 １−（２−クロロベンジル）−２−エチル−３−（１−
ヒドロキシ−２−メチルプロピル）インドール−６−カ
ルボキサミド mp : 169−172℃ NMR (CDCl3,δ) : 0.78 (3H,d,J=7Hz), 1.17 (3H,t,J=7
Hz), 1.23 (3H,d,J=7Hz), 2.41 (1H,m), 2.74 (2H,m),
4.60 (1H,m), 5.43 (2H,s), 6.14(1H,d,J=8Hz), 6.98
(1H,t,J=8Hz), 7.17 (1H,t,J=8Hz), 7.4-7.5 (2H,m),
7.76 (1H,s), 7.85 (1H,d,J=8Hz)Production Example 122 The following compound was produced in the same manner as in Production Example 121. 1- (2-chlorobenzyl) -2-ethyl-3- (1-
(Hydroxy-2-methylpropyl) indole-6-carboxamide mp: 169-172 ° C NMR (CDCl3 , δ): 0.78 (3H, d, J = 7Hz), 1.17 (3H, t, J = 7)
Hz), 1.23 (3H, d, J = 7Hz), 2.41 (1H, m), 2.74 (2H, m),
4.60 (1H, m), 5.43 (2H, s), 6.14 (1H, d, J = 8Hz), 6.98
(1H, t, J = 8Hz), 7.17 (1H, t, J = 8Hz), 7.4-7.5 (2H, m),
7.76 (1H, s), 7.85 (1H, d, J = 8Hz)
【０２９４】製造例123 ３−アセチル−１−（２−クロロベンジル）−２−プロ
ピルインドール−６−カルボキサミド（36.5mg）のエタ
ノール（５ml）懸濁液に、ヒドロキシルアミン塩酸塩
（70mg）および酢酸ナトリウム（200mg）を加え、混合
物を封管中100℃で加熱した。反応混合物を減圧下で蒸
発させ、つぎに、残留物を酢酸エチルで希釈し、水およ
び食塩水で洗った。有機層を硫酸ナトリウムで乾燥し、
減圧下で蒸発させた。残留物をジイソプロピルエーテル
を用いて粉末化して、１−（２−クロロベンジル）−３
−（１−ヒドロキシイミノエチル）−２−プロピルイン
ドール−６−カルボキサミド（32.7mg）を得た。 mp : 212−216℃ NMR (CDCl3,δ) : 0.94 (3H,t,J=7Hz), 1.56 (2H,m),
2.39 (3H,s), 2.80(2H,m), 5.45 (2H,s), 6.21 (1H,d,J
=8Hz), 6.99 (1H,t,J=8Hz), 7.20(1H,t,J=8Hz), 7.42
(1H,d,J=8Hz), 7.50 (1H,m), 7.70-7.78 (2H,m)Production Example 123 To a suspension of 3-acetyl-1- (2-chlorobenzyl) -2-propylindole-6-carboxamide (36.5 mg) in ethanol (5 ml) was added hydroxylamine hydrochloride (70 mg) and acetic acid. Sodium (200 mg) was added and the mixture was heated at 100 ° C. in a sealed tube. The reaction mixture was evaporated under reduced pressure, then the residue was diluted with ethyl acetate and washed with water and brine. The organic layer is dried over sodium sulfate,
Evaporated under reduced pressure. The residue was triturated with diisopropyl ether to give 1- (2-chlorobenzyl) -3.
-(1-Hydroxyiminoethyl) -2-propylindole-6-carboxamide (32.7 mg) was obtained. mp: 212-216 ° C NMR (CDCl3 , δ): 0.94 (3H, t, J = 7Hz), 1.56 (2H, m),
2.39 (3H, s), 2.80 (2H, m), 5.45 (2H, s), 6.21 (1H, d, J
= 8Hz), 6.99 (1H, t, J = 8Hz), 7.20 (1H, t, J = 8Hz), 7.42
(1H, d, J = 8Hz), 7.50 (1H, m), 7.70-7.78 (2H, m)
【０２９５】製造例124 １−（２−アミノベンジル）−３−イソブチリル−２−
プロピルインドール−６−カルボキサミド塩酸塩（111m
g）をクロロホルムに溶解させ、溶液を１Ｎ水酸化ナト
リウム水溶液で洗い、硫酸マグネシウムで乾燥し、減圧
下で蒸発させた。残留物をクロロホルム（３ml）に溶解
させ、つぎに、０℃で、メチルイソシアナート（1.5m
l）を加えた。20℃で２時間撹拌後、混合物を減圧下で
蒸発させた。残留物を酢酸エチル−テトラヒドロフラン
混合物に溶解させ、溶液を水および食塩水で洗い、硫酸
マグネシウムで乾燥し、減圧下で蒸発させた。結晶性残
留物を１,４−ジオキサン−ヘキサン混合物から再結晶
して、３−イソブチリル−１−［２−（３−メチルウレ
イド）ベンジル］−２−プロピルインドール−６−カル
ボキサミド（74mg）を無色結晶として得た。 mp : 222−223℃ IR (KBr) : 1648, 1617, 1557 cm-1 NMR (DMSO-d6,δ) : 0.91 (3H,t,J=7Hz), 1.18 (6H,d,J
=7Hz), 1.42-1.50(2H,m), 2.71 (3H,d,J=5Hz), 2.92-3.
00 (2H,m), 3.50-3.56 (1H,m),5.48 (2H,s), 5.99 (1H,
d,J=8Hz), 6.34-6.39 (1H,m), 6.86 (1H,t,J=7.5Hz),
7.18 (1H,t,J=7.5Hz), 7.28 (1H,s), 7.55 (1H,t,J=7.5
Hz),7.78 (1H,d,J=7.5Hz), 7.92-7.97 (3H,m), 8.21 (1
H,s) MASS (m/z) : 435 (M++1), 86 (bp)Production Example 124 1- (2-aminobenzyl) -3-isobutyryl-2-
Propylindole-6-carboxamide hydrochloride (111m
g) was dissolved in chloroform, the solution was washed with 1N aqueous sodium hydroxide solution, dried over magnesium sulfate and evaporated under reduced pressure. The residue was dissolved in chloroform (3 ml). Then, at 0 ° C., methyl isocyanate (1.5 m
l) was added. After stirring at 20 ° C. for 2 hours, the mixture was evaporated under reduced pressure. The residue was dissolved in an ethyl acetate-tetrahydrofuran mixture, the solution was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The crystalline residue was recrystallized from a 1,4-dioxane-hexane mixture to give 3-isobutyryl-1- [2- (3-methylureido) benzyl] -2-propylindole-6-carboxamide (74 mg) as colorless. Obtained as crystals. mp: 222-223 ° C IR (KBr): 1648, 1617, 1557 cm-1 NMR (DMSO-d6 , δ): 0.91 (3H, t, J = 7Hz), 1.18 (6H, d, J
= 7Hz), 1.42-1.50 (2H, m), 2.71 (3H, d, J = 5Hz), 2.92-3.
00 (2H, m), 3.50-3.56 (1H, m), 5.48 (2H, s), 5.99 (1H,
d, J = 8Hz), 6.34-6.39 (1H, m), 6.86 (1H, t, J = 7.5Hz),
7.18 (1H, t, J = 7.5Hz), 7.28 (1H, s), 7.55 (1H, t, J = 7.5
Hz), 7.78 (1H, d, J = 7.5Hz), 7.92-7.97 (3H, m), 8.21 (1
H, s) MASS (m / z): 435 (M+ +1), 86 (bp)
【０２９６】製造例125 １−（２−クロロベンジル）−２−プロピルインドール
−６−カルボン酸メチルエステル（200mg）のトリフル
オロ酢酸（２ml）溶液に、０℃で、濃硝酸（0.3ml）を
加えた。０℃で30分間撹拌後、反応混合物を酢酸エチル
と水とに分配する。有機層を炭酸ナトリウム水溶液、水
および食塩水で洗い、硫酸マグネシウムで乾燥し、減圧
下で蒸発させた。残留物を分取シリカゲル薄層クロマト
グラフィーに付し、酢酸エチル−ヘキサン（１：３）で
溶出して精製し、１−（２−クロロベンジル）−３−ニ
トロ−２−プロピルインドール−６−カルボン酸メチル
エステル（73mg）を淡黄色結晶として得た。 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.68 (2H,sexte
t,J=7Hz), 3.14-3.18(2H,m), 3.91 (3H,s), 5.13 (2H,
s), 6.32 (1H,d,J=8Hz), 7.08 (1H,t,J=8Hz), 7.27 (1
H,t,J=8Hz), 7.48 (1H,d,J=8Hz), 7.98 (1H,s), 8.08(1
H,d,J=8Hz), 8.43 (1H,d,J=8Hz)Production Example 125 To a solution of 1- (2-chlorobenzyl) -2-propylindole-6-carboxylic acid methyl ester (200 mg) in trifluoroacetic acid (2 ml) was added concentrated nitric acid (0.3 ml) at 0 ° C. added. After stirring at 0 ° C. for 30 minutes, the reaction mixture is partitioned between ethyl acetate and water. The organic layer was washed with aqueous sodium carbonate, water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography, eluting with ethyl acetate-hexane (1: 3), to give 1- (2-chlorobenzyl) -3-nitro-2-propylindole-6-. Carboxylic acid methyl ester (73 mg) was obtained as pale yellow crystals. NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.68 (2H, sexte
t, J = 7Hz), 3.14-3.18 (2H, m), 3.91 (3H, s), 5.13 (2H,
s), 6.32 (1H, d, J = 8Hz), 7.08 (1H, t, J = 8Hz), 7.27 (1
H, t, J = 8Hz), 7.48 (1H, d, J = 8Hz), 7.98 (1H, s), 8.08 (1
(H, d, J = 8Hz), 8.43 (1H, d, J = 8Hz)
【０２９７】製造例126 製造例54と同様にして、下記(1)〜(44)に記載の化合物
を製造した。 (1) １−（２−クロロベンジル）−２−（３−メトキシ
カルボニルプロピル）インドール−６−カルボン酸メチ
ルエステル NMR (CDCl3,δ) : 2.04 (2H,m), 2.88 (2H,t,J=7Hz),
2.69 (2H,t,J=7Hz),3.62 (3H,s), 3.89 (3H,s), 5.43
(2H,s), 6.14 (1H,d,J=8Hz), 6.46(1H,s), 7.01 (1H,t,
J=8Hz), 7.18 (1H,t,J=8Hz), 7.42 (1H,d,J=8Hz),7.59
(1H,d,J=8Hz), 7.80 (1H,d,J=8Hz), 7.90 (1H,s) (2) １−（２−クロロベンジル）−２−（２−メトキシ
カルボニルエチル）インドール−６−カルボン酸メチル
エステル NMR (CDCl3,δ) : 2.77 (2H,m), 2.98 (2H,m), 3.69 (3
H,s), 3.88 (3H,s),5.45 (2H,s), 6.16 (1H,d,J=8Hz),
6.41 (1H,s), 7.02 (1H,t,J=8Hz),7.19 (1H,t,J=8Hz),
7.42 (1H,d,J=8Hz), 7.60 (1H,d,J=8Hz), 7.81(1H,d,J=
8Hz), 7.91 (1H,s)Production Example 126 The following compounds (1) to (44) were produced in the same manner as in Production Example 54. (1) 1- (2-chlorobenzyl) -2- (3-methoxycarbonylpropyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.04 (2H, m), 2.88 (2H, t, J = 7Hz),
2.69 (2H, t, J = 7Hz), 3.62 (3H, s), 3.89 (3H, s), 5.43
(2H, s), 6.14 (1H, d, J = 8Hz), 6.46 (1H, s), 7.01 (1H, t,
J = 8Hz), 7.18 (1H, t, J = 8Hz), 7.42 (1H, d, J = 8Hz), 7.59
(1H, d, J = 8Hz), 7.80 (1H, d, J = 8Hz), 7.90 (1H, s) (2) 1- (2-chlorobenzyl) -2- (2-methoxycarbonylethyl) indole- 6-Carboxylic acid methyl ester NMR (CDCl3 , δ): 2.77 (2H, m), 2.98 (2H, m), 3.69 (3
H, s), 3.88 (3H, s), 5.45 (2H, s), 6.16 (1H, d, J = 8Hz),
6.41 (1H, s), 7.02 (1H, t, J = 8Hz), 7.19 (1H, t, J = 8Hz),
7.42 (1H, d, J = 8Hz), 7.60 (1H, d, J = 8Hz), 7.81 (1H, d, J =
8Hz), 7.91 (1H, s)
【０２９８】(3) １−（２−クロロベンジル）−３−イ
ソブチリル−２−プロピルインドール−７−カルボン酸
メチルエステル NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.79 (6H,d,J=7
Hz), 1.63 (2H,m),3.01 (2H,m), 3.52 (1H,m), 3.56 (3
H,s), 5.61 (2H,s), 6.08 (1H,d,J=8Hz), 6.98 (1H,t,J
=8Hz), 7.17 (1H,t,J=8Hz), 7.2-7.45 (3H,m),8.12 (1
H,d,J=8Hz) (4) １−（２−クロロベンジル）−３−イソブチリル−
２−プロピルインドール−５−カルボン酸メチルエステ
ル NMR (CDCl3,δ) : 1.03 (3H,t,J=8Hz), 1.34 (6H,d,J=8
Hz), 1.62 (2H,sextet,J=8Hz), 3.06-3.10 (2H,m), 3.6
4 (1H,septet,J=8Hz), 3.96 (3H,s), 5.47 (2H,s), 6.2
6 (1H,d,J=8Hz), 7.06 (1H,t,J=8Hz), 7.20 (1H,t,J=8H
z), 7.25 (1H,d,J=8Hz), 7.47 (1H,dd,J=1, 8Hz), 7.92
(1H,d,J=8Hz), 8.68 (1H,d,J=1Hz)(3) 1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole-7-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.02 (3H, t, J = 7 Hz), 1.79 (6H, d, J = 7
Hz), 1.63 (2H, m), 3.01 (2H, m), 3.52 (1H, m), 3.56 (3
H, s), 5.61 (2H, s), 6.08 (1H, d, J = 8Hz), 6.98 (1H, t, J
= 8Hz), 7.17 (1H, t, J = 8Hz), 7.2-7.45 (3H, m), 8.12 (1
(H, d, J = 8Hz) (4) 1- (2-chlorobenzyl) -3-isobutyryl-
2-propyl-indole-5-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.03 (3H, t, J = 8Hz), 1.34 (6H, d, J = 8
Hz), 1.62 (2H, sextet, J = 8Hz), 3.06-3.10 (2H, m), 3.6
4 (1H, septet, J = 8Hz), 3.96 (3H, s), 5.47 (2H, s), 6.2
6 (1H, d, J = 8Hz), 7.06 (1H, t, J = 8Hz), 7.20 (1H, t, J = 8H)
z), 7.25 (1H, d, J = 8Hz), 7.47 (1H, dd, J = 1,8Hz), 7.92
(1H, d, J = 8Hz), 8.68 (1H, d, J = 1Hz)
【０２９９】(5) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−イソブチリル−２−プロピル
インドール−５−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.05 (3H,t,J=8Hz), 1.32 (6H,d,J=8
Hz), 1.62 (2H,sextet,J=8Hz), 3.06 (2H,t,J=8Hz), 3.
63 (1H,septet,J=8Hz), 3.96(3H,s), 5.36 (2H,s), 5.7
4 (1H,s), 5.88 (2H,s), 6.92 (1H,s), 7.20(1H,d,J=10
Hz), 7.82 (1H,d,J=10Hz), 8.76 (1H,s) (6) １−（２−クロロベンジル）−２−プロピルインド
ール−４−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.78 (2H,m),
2.67 (2H,t,J=7Hz),3.99 (3H,s), 5.42 (2H,s), 6.18
(1H,d,J=8Hz), 7.01 (1H,t,J=8Hz),7.03 (1H,s), 7.11
(1H,t,J=8Hz), 7.18 (1H,t,J=8Hz), 7.30 (1H,d,J=8H
z), 7.43 (1H,d,J=8Hz), 7.89 (1H,d,J=8Hz)(5) 1- (6-chloro-3,4-methylenedioxybenzyl) -3-isobutyryl-2-propylindole-5-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.05 (3H, t, J = 8Hz), 1.32 (6H, d, J = 8
Hz), 1.62 (2H, sextet, J = 8Hz), 3.06 (2H, t, J = 8Hz), 3.
63 (1H, septet, J = 8Hz), 3.96 (3H, s), 5.36 (2H, s), 5.7
4 (1H, s), 5.88 (2H, s), 6.92 (1H, s), 7.20 (1H, d, J = 10
Hz), 7.82 (1H, d, J = 10 Hz), 8.76 (1H, s) (6) 1- (2-chlorobenzyl) -2-propylindole-4-carboxylic acid methyl ester NMR (CDCl3 , δ) : 1.01 (3H, t, J = 7Hz), 1.78 (2H, m),
2.67 (2H, t, J = 7Hz), 3.99 (3H, s), 5.42 (2H, s), 6.18
(1H, d, J = 8Hz), 7.01 (1H, t, J = 8Hz), 7.03 (1H, s), 7.11
(1H, t, J = 8Hz), 7.18 (1H, t, J = 8Hz), 7.30 (1H, d, J = 8H
z), 7.43 (1H, d, J = 8Hz), 7.89 (1H, d, J = 8Hz)
【０３００】(7) ９−（２−クロロベンジル）−８−オ
キソ−５,６,７,８−テトラヒドロカルバゾール−２−
カルボン酸メチルエステル NMR (CDCl3,δ) : 2.27 (2H,m), 2.67 (2H,t,J=7Hz),
3.11 (2H,t,J=7Hz),3.90 (3H,s), 5.95 (2H,s), 6.25
(1H,d,J=8Hz), 6.98 (1H,t,J=8Hz),7.15 (1H,t,J=8Hz),
7.40 (1H,d,J=8Hz), 7.74 (1H,d,J=8Hz), 7.84(1H,d,J
=8Hz), 7.99 (1H,s) (8) ９−（６−クロロ−３,４−メチレンジオキシベン
ジル）−８−オキソ−５,６,７,８−テトラヒドロカル
バゾール−２−カルボン酸メチルエステル NMR (CDCl3,δ) : 2.18 (2H,m), 2.63 (2H,t,J=7Hz),
3.07 (2H,t,J=7Hz),3.84 (3H,s), 5.68 (1H,s), 5.83
(2H,s), 5.96 (2H,s), 7.18 (1H,s),7.84 (1H,d,J=8H
z), 7.92 (1H,d,J=8Hz), 8.03 (1H,s)(7) 9- (2-chlorobenzyl) -8-oxo-5,6,7,8-tetrahydrocarbazole-2-
Carboxylic acid methyl ester NMR (CDCl3 , δ): 2.27 (2H, m), 2.67 (2H, t, J = 7Hz),
3.11 (2H, t, J = 7Hz), 3.90 (3H, s), 5.95 (2H, s), 6.25
(1H, d, J = 8Hz), 6.98 (1H, t, J = 8Hz), 7.15 (1H, t, J = 8Hz),
7.40 (1H, d, J = 8Hz), 7.74 (1H, d, J = 8Hz), 7.84 (1H, d, J
= 8Hz), 7.99 (1H, s) (8) Methyl 9- (6-chloro-3,4-methylenedioxybenzyl) -8-oxo-5,6,7,8-tetrahydrocarbazole-2-carboxylate Ester NMR (CDCl3 , δ): 2.18 (2H, m), 2.63 (2H, t, J = 7Hz),
3.07 (2H, t, J = 7Hz), 3.84 (3H, s), 5.68 (1H, s), 5.83
(2H, s), 5.96 (2H, s), 7.18 (1H, s), 7.84 (1H, d, J = 8H
z), 7.92 (1H, d, J = 8Hz), 8.03 (1H, s)
【０３０１】(9) １−（４−ブロモ−２−クロロベンジ
ル）−３−イソブチリル−２−プロピルインドール−６
−カルボン酸メチルエステル mp : 65−67℃ IR (KBr) : 1715, 1705, 1656, 1456, 1433 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.52-1.64 (2H,m), 2.99-3.05 (2H,m), 3.51-3.60
(1H,m), 3.92 (3H,s), 5.45 (2H,s),6.09 (1H,d,J=7.5
Hz), 7.18 (1H,d,J=7.5Hz), 7.66 (1H,s), 7.90 (1H,
s), 7.99 (2H,s) MASS (m/z) : 492 (M++2) (10) １−（２−アセトアミドベンジル）−３−イソブ
チリル−２−プロピルインドール−６−カルボキサミド mp : 235−236℃ IR (KBr) : 1693, 1656, 1457 cm-1 NMR (CDCl3,δ) : 0.91 (3H,t,J=7Hz), 1.18 (6H,d,J=7
Hz), 1.39-1.50 (2H,m), 2.17 (3H,s), 2.92-2.99 (2H,
m), 3.50-3.59 (1H,m), 5.49 (2H,s),6.07 (1H,d,J=7.5
Hz), 7.00 (1H,t,J=7.5Hz), 7.21-7.29 (2H,m), 7.39(1
H,d,J=7.5Hz), 7.79 (1H,d,J=7.5Hz), 7.92-7.96 (3H,
m), 9.85 (1H,s) MASS (m/z) : 420 (M++1), 86 (bp)(9) 1- (4-bromo-2-chlorobenzyl) -3-isobutyryl-2-propylindole-6
-Carboxylic acid methyl ester mp: 65-67 ° C IR (KBr): 1715, 1705, 1656, 1456, 1433 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.30 (6H , d, J = 7
Hz), 1.52-1.64 (2H, m), 2.99-3.05 (2H, m), 3.51-3.60
(1H, m), 3.92 (3H, s), 5.45 (2H, s), 6.09 (1H, d, J = 7.5
Hz), 7.18 (1H, d, J = 7.5Hz), 7.66 (1H, s), 7.90 (1H,
s), 7.99 (2H, s) MASS (m / z): 492 (M++ 2) (10) 1- (2-acetamidobenzyl) -3-isobutyryl-2-propylindole-6-carboxamide mp: 235 -236 ° C IR (KBr): 1693, 1656, 1457 cm-1 NMR (CDCl3 , δ): 0.91 (3H, t, J = 7Hz), 1.18 (6H, d, J = 7
Hz), 1.39-1.50 (2H, m), 2.17 (3H, s), 2.92-2.99 (2H,
m), 3.50-3.59 (1H, m), 5.49 (2H, s), 6.07 (1H, d, J = 7.5
Hz), 7.00 (1H, t, J = 7.5Hz), 7.21-7.29 (2H, m), 7.39 (1
H, d, J = 7.5Hz), 7.79 (1H, d, J = 7.5Hz), 7.92-7.96 (3H,
m), 9.85 (1H, s) MASS (m / z): 420 (M+ +1), 86 (bp)
【０３０２】(11) １−（２−クロロベンジル）−３−
ホルミルインドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 3.93 (3H,s), 5.52 (2H,s), 6.88 (1
H,dd,J=1, 8Hz),7.21 (1H,dt,J=1, 8Hz), 7.32 (1H,dt,
J=1, 8Hz), 7.49 (1H,dd,J=1,8Hz), 7.82 (1H,s), 8.02
(1H,dd,J=1, 8Hz), 8.13 (1H,d,J=1Hz), 8.36(1H,d,J=
8Hz), 10.0 (1H,s) (12) ３−アセチル−１−（２−クロロベンジル）−２
−メチルインドール−６−カルボン酸メチルエステル この化合物は、精製せずに、そのまま直ちに使用した。(11) 1- (2-chlorobenzyl) -3-
Formyl-indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 3.93 (3H, s), 5.52 (2H, s), 6.88 (1
H, dd, J = 1,8Hz), 7.21 (1H, dt, J = 1,8Hz), 7.32 (1H, dt,
J = 1, 8Hz), 7.49 (1H, dd, J = 1,8Hz), 7.82 (1H, s), 8.02
(1H, dd, J = 1,8Hz), 8.13 (1H, d, J = 1Hz), 8.36 (1H, d, J =
8Hz), 10.0 (1H, s) (12) 3-acetyl-1- (2-chlorobenzyl) -2
-Methylindole-6-carboxylic acid methyl ester This compound was used directly without purification.
【０３０３】(13) １−（２−クロロベンジル）−２−
メチル−３−プロピオニルインドール−６−カルボン酸
メチルエステル NMR (CDCl3,δ) : 1.31 (3H,t,J=7Hz), 2.70 (3H,s),
3.09 (2H,q,J=7Hz),3.90 (3H,s), 5.50 (2H,s), 6.22
(1H,d,J=8Hz), 7.04 (1H,t,J=8Hz),7.24 (1H,t,J=8Hz),
7.46 (1H,d,J=8Hz), 7.92-7.98 (2H,m), 8.08 (1H,d,J
=8Hz) (14) １−（２−クロロベンゾ［ｂ］チオフェン−３−
イルメチル）−３−イソブチリル−２−メチルインドー
ル−６−カルボン酸メチルエステル NMR (DMSO-d6,δ) : 1.14 (6H,d,J=7Hz), 2.72 (3H,s),
3.48 (1H,m), 3.81(3H,s), 5.91 (2H,s), 7.3-7.5 (3
H,m), 7.80 (1H,d,J=8Hz), 7.98 (1H,d,J=8Hz), 8.06
(1H,d,J=8Hz), 8.19 (1H,s)(13) 1- (2-chlorobenzyl) -2-
Methyl-3-propionyl-indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.31 (3H, t, J = 7Hz), 2.70 (3H, s),
3.09 (2H, q, J = 7Hz), 3.90 (3H, s), 5.50 (2H, s), 6.22
(1H, d, J = 8Hz), 7.04 (1H, t, J = 8Hz), 7.24 (1H, t, J = 8Hz),
7.46 (1H, d, J = 8Hz), 7.92-7.98 (2H, m), 8.08 (1H, d, J
= 8Hz) (14) 1- (2-chlorobenzo [b] thiophene-3-
Ylmethyl) -3-isobutyryl-2-methylindole-6-carboxylic acid methyl ester NMR (DMSO-d6 , δ): 1.14 (6H, d, J = 7Hz), 2.72 (3H, s),
3.48 (1H, m), 3.81 (3H, s), 5.91 (2H, s), 7.3-7.5 (3
H, m), 7.80 (1H, d, J = 8Hz), 7.98 (1H, d, J = 8Hz), 8.06
(1H, d, J = 8Hz), 8.19 (1H, s)
【０３０４】(15) １−（ベンゾチアゾール−２−イル
メチル）−２−エチル−３−イソブチリルインドール−
６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.28 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 3.24 (2H,q,J=7Hz), 3.53 (1H,m), 3.91 (3H,s),
5.82 (2H,s), 7.25-7.53 (2H,m),7.72 (1H,m), 7.8-8.1
(3H,m), 8.18 (1H,s) (16) １−（ベンゾ［ｂ］チオフェン−５−イルメチ
ル）−３−イソブチリル−２−プロピルインドール−６
−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.32 (6H,d,J=7
Hz), 1.62 (2H,m),3.13 (2H,m), 3.57 (1H,m), 3.87 (3
H,s), 5.57 (2H,s), 7.03 (1H,d,J=8Hz), 7.18 (1H,d,J
=6Hz), 7.29 (1H,s), 7.44 (1H,d,J=6Hz), 7.79(1H,d,J
=8Hz), 7.94 (2H,s), 8.02 (1H,s)(15) 1- (benzothiazol-2-ylmethyl) -2-ethyl-3-isobutyrylindole-
6-Carboxylic acid methyl ester NMR (CDCl3 , δ): 1.28 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 3.24 (2H, q, J = 7Hz), 3.53 (1H, m), 3.91 (3H, s),
5.82 (2H, s), 7.25-7.53 (2H, m), 7.72 (1H, m), 7.8-8.1
(3H, m), 8.18 (1H, s) (16) 1- (benzo [b] thiophen-5-ylmethyl) -3-isobutyryl-2-propylindole-6
- carboxylic acid methyl esterNMR (CDCl 3, δ): 1.02 (3H, t, J = 7Hz), 1.32 (6H, d, J = 7
Hz), 1.62 (2H, m), 3.13 (2H, m), 3.57 (1H, m), 3.87 (3
H, s), 5.57 (2H, s), 7.03 (1H, d, J = 8Hz), 7.18 (1H, d, J
= 6Hz), 7.29 (1H, s), 7.44 (1H, d, J = 6Hz), 7.79 (1H, d, J
= 8Hz), 7.94 (2H, s), 8.02 (1H, s)
【０３０５】(17) １−アリル−３−イソブチリル−２
−プロピルインドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.07 (3H,t,J=7Hz), 1.28 (6H,d,J=7
Hz), 1.69 (2H,m),3.12 (2H,m), 3.54 (1H,m), 3.94 (3
H,s), 4.84 (2H,m), 4.87 (1H,m),5.22 (1H,m), 5.98
(1H,m), 7.89 (1H,d,J=8Hz), 7.94 (1H,d,J=8Hz),8.04
(1H,s) (18) １−（２−クロロベンジル）−３−イソブチリル
−２−（１−プロペニル）インドール−６−カルボン酸
メチルエステル NMR (CDCl3,δ) : 1.23 (6H,d,J=7Hz), 1.93 (3H,d,J=7
Hz), 3.51 (1H,m),3.89 (3H,s), 5.50 (2H,s), 6.41 (1
H,m), 6.42 (1H,d,J=8Hz), 6.73(1H,d,J=16Hz), 7.07
(1H,t,J=8Hz), 7.23 (1H,t,J=8Hz), 7.47 (1H,d,J=8H
z), 7.89 (1H,s), 7.95 (1H,d,J=8Hz), 8.18 (1H,d,J=8
Hz)(17) 1-allyl-3-isobutyryl-2
- propyl-indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.07 (3H, t, J = 7Hz), 1.28 (6H, d, J = 7
Hz), 1.69 (2H, m), 3.12 (2H, m), 3.54 (1H, m), 3.94 (3
H, s), 4.84 (2H, m), 4.87 (1H, m), 5.22 (1H, m), 5.98
(1H, m), 7.89 (1H, d, J = 8Hz), 7.94 (1H, d, J = 8Hz), 8.04
(1H, s) (18) 1- (2-chlorobenzyl) -3-isobutyryl-2- (1-propenyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.23 (6H, d, J = 7Hz), 1.93 (3H, d, J = 7
Hz), 3.51 (1H, m), 3.89 (3H, s), 5.50 (2H, s), 6.41 (1
H, m), 6.42 (1H, d, J = 8Hz), 6.73 (1H, d, J = 16Hz), 7.07
(1H, t, J = 8Hz), 7.23 (1H, t, J = 8Hz), 7.47 (1H, d, J = 8H
z), 7.89 (1H, s), 7.95 (1H, d, J = 8Hz), 8.18 (1H, d, J = 8
Hz)
【０３０６】(19) ２−（１−アセトキシプロピル）−
１−（２−クロロベンジル）−３−イソブチリルインド
ール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.2-1.35 (9H,
m), 1.9-2.1 (2H,m),3.59 (1H,m), 3.89 (3H,s), 5.61
(1H,d,J=17Hz), 5.79 (1H,d,J=17Hz),6.04 (1H,d,J=8H
z), 6.71 (1H,m), 7.01 (1H,t,J=8Hz), 7.21 (1H,t,J=8
Hz), 7.47 (1H,d,J=8Hz), 7.87 (1H,s), 7.92 (1H,d,J=
8Hz), 7.97(1H,d,J=8Hz) (20) ３−（３,３−ジメチルブタノイル）−１−（２−
クロロベンジル）インドール−６−カルボン酸メチルエ
ステル NMR (CDCl3,δ) : 1.09 (9H,s), 2.69 (2H,s), 3.93 (3
H,s), 5.50 (2H,s),6.73 (1H,d,J=8Hz), 7.17 (1H,t,J=
8Hz), 7.28 (1H,t,J=8Hz), 7.47(1H,d,J=8Hz), 7.82 (1
H,s), 8.00 (1H,d,J=8Hz), 8.08 (1H,s), 8.53(1H,d,J=
8Hz)(19) 2- (1-acetoxypropyl)-
1- (2-chlorobenzyl) -3-isobutyrylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.04 (3H, t, J = 7 Hz), 1.2-1.35 (9H,
m), 1.9-2.1 (2H, m), 3.59 (1H, m), 3.89 (3H, s), 5.61
(1H, d, J = 17Hz), 5.79 (1H, d, J = 17Hz), 6.04 (1H, d, J = 8H
z), 6.71 (1H, m), 7.01 (1H, t, J = 8Hz), 7.21 (1H, t, J = 8
Hz), 7.47 (1H, d, J = 8Hz), 7.87 (1H, s), 7.92 (1H, d, J =
8Hz), 7.97 (1H, d, J = 8Hz) (20) 3- (3,3-dimethylbutanoyl) -1- (2-
Chlorobenzyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.09 (9H, s), 2.69 (2H, s), 3.93 (3
H, s), 5.50 (2H, s), 6.73 (1H, d, J = 8Hz), 7.17 (1H, t, J =
8Hz), 7.28 (1H, t, J = 8Hz), 7.47 (1H, d, J = 8Hz), 7.82 (1
H, s), 8.00 (1H, d, J = 8Hz), 8.08 (1H, s), 8.53 (1H, d, J =
8Hz)
【０３０７】(21) １−（２−クロロベンジル）−３−
イソブチリル−２−プロピルインドール−６−イル酢酸
エチルエステル IR (ニート) : 1730, 1655 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.20 (3H,t,J=7
Hz), 1.29 (6H,d,J=7Hz), 1.55-1.65 (2H,m), 3.01-3.0
8 (2H,m), 3.54-3.60 (1H,m), 3.69(2H,s), 4.11 (2H,
q,J=7Hz), 5.44 (2H,s), 6.30 (1H,d,J=7.5Hz),7.03-7.
10 (2H,m), 7.21 (2H,d,J=7.5Hz), 7.46 (1H,d,J=7.5H
z), 7.89(1H,d,J=7.5Hz) MASS (m/z) : 440 (M++1), 74 (bp) (22) １−（６−クロロ−３,４−メチレンジオキシベン
ジル）−３−イソブチリル−２−プロピルインドール−
６−イル酢酸メチルエステル mp : 119−120.5℃ IR (KBr) : 1744, 1735, 1732, 1644, 1508 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.55-1.65 (2H,m), 3.00-3.07 (2H,m), 3.53-3.61
(1H,m), 3.70 (3H,s), 3.72 (2H,s),5.33 (2H,s), 5.8
0 (2H,s), 5.91 (2H,s), 6.93 (1H,s), 7.01 (1H,s),7.
21 (1H,d,J=7.5Hz), 7.89 (1H,d,J=7.5Hz) MASS (m/z) : 470 (M++1), 74 (bp)(21) 1- (2-chlorobenzyl) -3-
Isobutyryl-2-propylindol-6-ylacetic acid ethyl ester IR (neat): 1730, 1655 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.20 (3H, t, J = 7
Hz), 1.29 (6H, d, J = 7Hz), 1.55-1.65 (2H, m), 3.01-3.0
8 (2H, m), 3.54-3.60 (1H, m), 3.69 (2H, s), 4.11 (2H, m
q, J = 7Hz), 5.44 (2H, s), 6.30 (1H, d, J = 7.5Hz), 7.03-7.
10 (2H, m), 7.21 (2H, d, J = 7.5Hz), 7.46 (1H, d, J = 7.5H
z), 7.89 (1H, d, J = 7.5 Hz) MASS (m / z): 440 (M++ 1), 74 (bp) (22) 1- (6-chloro-3,4-methylenedioxy (Benzyl) -3-isobutyryl-2-propylindole-
6-ylacetic acid methyl ester mp: 119-120.5 ° C IR (KBr): 1744, 1735, 1732, 1644, 1508 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.29 ( 6H, d, J = 7
Hz), 1.55-1.65 (2H, m), 3.00-3.07 (2H, m), 3.53-3.61
(1H, m), 3.70 (3H, s), 3.72 (2H, s), 5.33 (2H, s), 5.8
0 (2H, s), 5.91 (2H, s), 6.93 (1H, s), 7.01 (1H, s), 7.
21 (1H, d, J = 7.5Hz), 7.89 (1H, d, J = 7.5Hz) MASS (m / z): 470 (M+ +1), 74 (bp)
【０３０８】(23) １−（２−クロロベンジル）−２−
プロピルインドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.75 (2H,m),
2.62 (2H,t,J=7Hz),3.87 (3H,s), 5.42 (2H,s), 6.16
(1H,d,J=8Hz), 6.42 (1H,s), 7.01(1H,t,J=8Hz), 7.19
(1H,t,J=8Hz), 7.42 (1H,t,J=8Hz), 7.58 (1H,t,J=8H
z), 7.79 (1H,d,J=8Hz), 8.92 (1H,s) (24) １−（２−ブロモベンジル）−２−プロピルイン
ドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 0.99 (3H,t,J=7Hz), 1.74 (2H,m),
2.59 (2H,t,J=7Hz),3.88 (3H,s), 5.37 (2H,s), 6.12
(1H,d,J=8Hz), 6.42 (1H,s), 7.0-7.15 (2H,m), 7.52-
7.65 (2H,m), 7.79 (1H,d,J=8Hz), 7.89 (1H,s)(23) 1- (2-chlorobenzyl) -2-
Propyl indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.02 (3H, t, J = 7Hz), 1.75 (2H, m),
2.62 (2H, t, J = 7Hz), 3.87 (3H, s), 5.42 (2H, s), 6.16
(1H, d, J = 8Hz), 6.42 (1H, s), 7.01 (1H, t, J = 8Hz), 7.19
(1H, t, J = 8Hz), 7.42 (1H, t, J = 8Hz), 7.58 (1H, t, J = 8H)
z), 7.79 (1 H, d, J = 8 Hz), 8.92 (1 H, s) (24) 1- (2-bromobenzyl) -2-propylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ) : 0.99 (3H, t, J = 7Hz), 1.74 (2H, m),
2.59 (2H, t, J = 7Hz), 3.88 (3H, s), 5.37 (2H, s), 6.12
(1H, d, J = 8Hz), 6.42 (1H, s), 7.0-7.15 (2H, m), 7.52-
7.65 (2H, m), 7.79 (1H, d, J = 8Hz), 7.89 (1H, s)
【０３０９】(25) ２−アセチル−１−（２−クロロベ
ンジル）−３−メチルインドール−６−カルボン酸メチ
ルエステル NMR (CDCl3,δ) : 2.61 (3H,s), 2.71 (3H,s), 3.90 (3
H,s), 5.82 (2H,s),6.19 (1H,d,J=8Hz), 6.97 (1H,t,J=
8Hz), 7.14 (1H,t,J=8Hz), 7.41 (1H,d,J=8Hz), 7.79
(1H,d,J=8Hz), 7.86 (1H,d,J=8Hz), 7.99 (1H,s) (26) ２−クロロ−１−（２−クロロベンジル）−３−
エチルインドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.29 (3H,t,J=7Hz), 2.83 (2H,q,J=7
Hz), 3.90 (3H,s),5.50 (2H,s), 6.29 (1H,d,J=8Hz),
7.04 (1H,t,J=8Hz), 7.19 (1H,t,J=8Hz), 7.42 (1H,d,J
=8Hz), 7.61 (1H,d,J=8Hz), 7.83 (1H,d,J=8Hz),7.90
(1H,s)(25) 2-acetyl-1- (2-chlorobenzyl) -3-methylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.61 (3H, s), 2.71 (3H, s) ), 3.90 (3
H, s), 5.82 (2H, s), 6.19 (1H, d, J = 8Hz), 6.97 (1H, t, J =
8Hz), 7.14 (1H, t, J = 8Hz), 7.41 (1H, d, J = 8Hz), 7.79
(1H, d, J = 8Hz), 7.86 (1H, d, J = 8Hz), 7.99 (1H, s) (26) 2-chloro-1- (2-chlorobenzyl) -3-
Ethyl indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.29 (3H, t, J = 7Hz), 2.83 (2H, q, J = 7
Hz), 3.90 (3H, s), 5.50 (2H, s), 6.29 (1H, d, J = 8Hz),
7.04 (1H, t, J = 8Hz), 7.19 (1H, t, J = 8Hz), 7.42 (1H, d, J
= 8Hz), 7.61 (1H, d, J = 8Hz), 7.83 (1H, d, J = 8Hz), 7.90
(1H, s)
【０３１０】(27) １−（２−クロロベンジル）−２−
プロピオニル−３−プロピルインドール−６−カルボン
酸メチルエステル NMR (CDCl3,δ) : 1.07 (3H,t,J=7Hz), 1.17 (3H,t,J=7
Hz), 1.78 (2H,m),2.94 (2H,q,J=7Hz), 3.09 (2H,m),
3.89 (3H,s), 5.72 (2H,s), 6.23(1H,d,J=8Hz), 6.98
(1H,t,J=8Hz), 7.15 (1H,t,J=8Hz), 7.39 (1H,d,J=8H
z), 7.76 (1H,d,J=8Hz), 7.83 (1H,d,J=8Hz), 7.96 (1
H,s) (28) １−（２−クロロベンジル）−２−イソブチリル
−３−プロピルインドール−６−カルボン酸メチルエス
テル NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.11 (6H,d,J=7
Hz), 1.75 (2H,m),3.02 (2H,m), 3.35 (1H,m), 3.89 (3
H,s), 5.64 (2H,s), 6.28 (1H,d,J=8Hz), 6.99 (1H,t,J
=8Hz), 7.16 (1H,t,J=8Hz), 7.38 (1H,d,J=8Hz),7.73
(1H,d,J=8Hz), 7.84 (1H,d,J=8Hz), 7.96 (1H,s)(27) 1- (2-chlorobenzyl) -2-
Propionyl-3-propyl-indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.07 (3H, t, J = 7Hz), 1.17 (3H, t, J = 7
Hz), 1.78 (2H, m), 2.94 (2H, q, J = 7Hz), 3.09 (2H, m),
3.89 (3H, s), 5.72 (2H, s), 6.23 (1H, d, J = 8Hz), 6.98
(1H, t, J = 8Hz), 7.15 (1H, t, J = 8Hz), 7.39 (1H, d, J = 8H
z), 7.76 (1H, d, J = 8Hz), 7.83 (1H, d, J = 8Hz), 7.96 (1
H, s) (28) 1- (2- chlorobenzyl) -2-isobutyryl-3-propyl-indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 1.03 (3H, t, J = 7Hz), 1.11 (6H, d, J = 7
Hz), 1.75 (2H, m), 3.02 (2H, m), 3.35 (1H, m), 3.89 (3
H, s), 5.64 (2H, s), 6.28 (1H, d, J = 8Hz), 6.99 (1H, t, J
= 8Hz), 7.16 (1H, t, J = 8Hz), 7.38 (1H, d, J = 8Hz), 7.73
(1H, d, J = 8Hz), 7.84 (1H, d, J = 8Hz), 7.96 (1H, s)
【０３１１】(29) １−（２−クロロベンジル）−３−
（３−オキソ−１−ブテニル）インドール−６−カルボ
ン酸メチルエステル NMR (CDCl3,δ) : 2.38 (3H,s), 3.93 (3H,s), 5.48 (2
H,s), 6.7-6.8 (2H,m), 7.17 (1H,t,J=8Hz), 7.28 (1H,
t,J=8Hz), 7.47 (1H,d,J=8Hz), 7.54(1H,s), 7.74 (1H,
d,J=15Hz), 7.96 (1H,s), 8.11 (1H,s) (30) ４−（２−クロロベンジル）−３−オキソ−１,
２,３,４−テトラヒドロシクロペンタ［ｂ］インドール
−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 3.06 (2H,m), 3.17 (2H,m), 3.92 (3
H,s), 5.72 (2H,s),6.59 (1H,d,J=8Hz), 7.06 (1H,t,J=
8Hz), 7.19 (1H,t,J=8Hz), 7.42(1H,d,J=8Hz), 7.78 (1
H,d,J=8Hz), 7.87 (1H,d,J=8Hz), 8.04 (1H,s)(29) 1- (2-chlorobenzyl) -3-
(3-oxo-1-butenyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 2.38 (3H, s), 3.93 (3H, s), 5.48 (2
H, s), 6.7-6.8 (2H, m), 7.17 (1H, t, J = 8Hz), 7.28 (1H,
t, J = 8Hz), 7.47 (1H, d, J = 8Hz), 7.54 (1H, s), 7.74 (1H,
d, J = 15Hz), 7.96 (1H, s), 8.11 (1H, s) (30) 4- (2-chlorobenzyl) -3-oxo-1,
2,3,4-tetrahydrocyclopenta [b] indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 3.06 (2H, m), 3.17 (2H, m), 3.92 (3
H, s), 5.72 (2H, s), 6.59 (1H, d, J = 8Hz), 7.06 (1H, t, J =
8Hz), 7.19 (1H, t, J = 8Hz), 7.42 (1H, d, J = 8Hz), 7.78 (1
(H, d, J = 8Hz), 7.87 (1H, d, J = 8Hz), 8.04 (1H, s)
【０３１２】(31) ４−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−オキソ−１,２,３,４−テト
ラヒドロシクロペンタ［ｂ］インドール−６−カルボン
酸メチルエステル NMR (CDCl3,δ) : 3.06 (3H,m), 3.14 (2H,m), 3.94 (3
H,s), 5.60 (2H,s),5.88 (2H,s), 6.11 (1H,s), 6.88
(1H,s), 7.76 (1H,d,J=8Hz), 7.86(1H,d,J=8Hz), 8.09
(1H,s) (32) １−（２−クロロベンジル）−３−シクロプロパ
ンカルボニル−２−プロピルインドール−６−カルボキ
サミド mp : 162−163.5℃ IR (KBr) : 1675, 1612, 1444, 1383 cm-1 NMR (DMSO-d6,δ) : 0.90 (3H,t,J=7Hz), 1.08 (4H,d,J
=7Hz), 1.48 (2H,sextet,J=7Hz), 2.65-2.72 (1H,m),
3.00 (2H,t,J=7Hz), 5.62 (2H,s),6.21 (1H,d,J=8Hz),
7.18 (1H,t,J=8Hz), 7.32 (1H,t,J=8Hz), 7.58(1H,d,J=
8Hz), 7.80 (1H,d,J=8Hz), 7.93 (1H,s), 8.01 (1H,s),
8.10(1H,d,J=7Hz) MASS (m/z) : 395 (M++1), 74 (bp)(31) 4- (6-Chloro-3,4-methylenedioxybenzyl) -3-oxo-1,2,3,4-tetrahydrocyclopenta [b] indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 3.06 (3H, m), 3.14 (2H, m), 3.94 (3
H, s), 5.60 (2H, s), 5.88 (2H, s), 6.11 (1H, s), 6.88
(1H, s), 7.76 (1H, d, J = 8Hz), 7.86 (1H, d, J = 8Hz), 8.09
(1H, s) (32) 1- (2-chlorobenzyl) -3-cyclopropanecarbonyl-2-propylindole-6-carboxamide mp: 162-13.5 ° C IR (KBr): 1675, 1612, 1444, 1383 cm-1 NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 7Hz), 1.08 (4H, d, J
= 7Hz), 1.48 (2H, sextet, J = 7Hz), 2.65-2.72 (1H, m),
3.00 (2H, t, J = 7Hz), 5.62 (2H, s), 6.21 (1H, d, J = 8Hz),
7.18 (1H, t, J = 8Hz), 7.32 (1H, t, J = 8Hz), 7.58 (1H, d, J =
8Hz), 7.80 (1H, d, J = 8Hz), 7.93 (1H, s), 8.01 (1H, s),
8.10 (1H, d, J = 7Hz) MASS (m / z): 395 (M+ +1), 74 (bp)
【０３１３】(33) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−シクロプロパンカルボニル−
２−プロピルインドール−６−カルボキサミド mp : 162−163.5℃ IR (KBr) : 1675, 1612, 1444, 1383 cm-1 NMR (DMSO-d6,δ) : 0.90 (3H,t,J=7Hz), 1.08 (4H,d,J
=7Hz), 1.48 (2H,sextet,J=7Hz), 2.65-2.72 (1H,m),
3.00 (2H,t,J=7Hz), 5.62 (2H,s),6.21 (1H,d,J=8Hz),
7.18 (1H,t,J=8Hz), 7.32 (1H,t,J=8Hz), 7.58(1H,d,J=
8Hz), 7.80 (1H,d,J=8Hz), 7.93 (1H,s), 8.01 (1H,s),
8.10(1H,d,J=7Hz) MASS (m/z) : 395 (M++1), 74 (bp) (34) １−（２−クロロベンジル）−３−シクロブタン
カルボニル−２−プロピルインドール−６−カルボキサ
ミド mp : 162−165℃ IR (KBr) : 1660, 1654, 1445, 1437 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.62 (2H,sexte
t,J=7Hz), 1.95-2.14(2H,m), 2.35-2.52 (4H,m), 3.05-
3.10 (2H,m), 4.05 (1H,quintet,J=7Hz), 5.50 (2H,s),
6.22 (1H,d,J=7.5Hz), 7.04 (1H,t,J=7.5Hz),7.21 (1
H,t,J=7.5Hz), 7.47 (1H,d,J=7.5Hz), 7.63 (1H,d,J=7.
5Hz),7.82 (1H,s), 7.97 (1H,d,J=7.5Hz) MASS (m/z) : 409 (M++1), 74 (bp)(33) 1- (6-chloro-3,4-methylenedioxybenzyl) -3-cyclopropanecarbonyl-
2-propylindole-6-carboxamide mp: 162-163.5 ° C IR (KBr): 1675, 1612, 1444, 1383 cm-1 NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 7Hz), 1.08 (4H, d, J
= 7Hz), 1.48 (2H, sextet, J = 7Hz), 2.65-2.72 (1H, m),
3.00 (2H, t, J = 7Hz), 5.62 (2H, s), 6.21 (1H, d, J = 8Hz),
7.18 (1H, t, J = 8Hz), 7.32 (1H, t, J = 8Hz), 7.58 (1H, d, J =
8Hz), 7.80 (1H, d, J = 8Hz), 7.93 (1H, s), 8.01 (1H, s),
8.10 (1H, d, J = 7 Hz) MASS (m / z): 395 (M++ 1), 74 (bp) (34) 1- (2-chlorobenzyl) -3-cyclobutanecarbonyl-2-propylindole -6-carboxamide mp: 162-165 ° C IR (KBr): 1660, 1654, 1445, 1437 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.62 (2H, sexte
t, J = 7Hz), 1.95-2.14 (2H, m), 2.35-2.52 (4H, m), 3.05-
3.10 (2H, m), 4.05 (1H, quintet, J = 7Hz), 5.50 (2H, s),
6.22 (1H, d, J = 7.5Hz), 7.04 (1H, t, J = 7.5Hz), 7.21 (1
H, t, J = 7.5Hz), 7.47 (1H, d, J = 7.5Hz), 7.63 (1H, d, J = 7.
5Hz), 7.82 (1H, s), 7.97 (1H, d, J = 7.5Hz) MASS (m / z): 409 (M+ +1), 74 (bp)
【０３１４】(35) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−シクロブタンカルボニル−２
−プロピルインドール−６−カルボキサミド mp : 240−241℃ IR (KBr) : 1658, 1636, 1503, 1482, 1451 cm-1 NMR (DMSO-d6,δ) : 0.94 (3H,t,J=7Hz), 1.49 (2H,sex
tet,J=7Hz), 1.79-1.90 (1H,m), 1.96-2.07 (1H,m), 2.
24-2.33 (4H,m), 3.03 (2H,t,J=7Hz), 4.07 (1H,quinte
t,J=7Hz), 5.51 (2H,s), 5.65 (1H,s), 6.00(2H,s), 7.
24 (1H,s), 7.31 (1H,br s), 7.79 (1H,d,J=7.5Hz), 7.
94(1H,br s), 7.95 (1H,d,J=7.5Hz), 8.00 (1H,s) MASS (m/z) : 453 (M++1), 85 (bp) (36) １−（２−クロロベンジル）−３−シクロペンタ
ンカルボニル−２−プロピルインドール−６−カルボキ
サミド mp : 201.5−202.5℃ IR (KBr) : 1654, 1607, 1447, 1437, 1387 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.59-1.82 (6H,
m), 1.99-2.07 (4H,m), 3.02-3.09 (2H,m), 3.79 (1H,q
uintet,J=7Hz), 5.52 (2H,s), 6.23(1H,d,J=7.5Hz), 7.
05 (1H,t,J=7.5Hz), 7.22 (1H,t,J=7.5Hz), 7.47(1H,d,
J=7.5Hz), 7.63 (1H,d,J=7.5Hz), 7.86 (1H,s), 8.04
(1H,d,J=7.5Hz) MASS (m/z) : 423 (M++1), 74 (bp)(35) 1- (6-chloro-3,4-methylenedioxybenzyl) -3-cyclobutanecarbonyl-2
-Propylindole-6-carboxamide mp: 240-241 ° C IR (KBr): 1658, 1636, 1503, 1482, 1451 cm-1 NMR (DMSO-d6 , δ): 0.94 (3H, t, J = 7Hz) , 1.49 (2H, sex
tet, J = 7Hz), 1.79-1.90 (1H, m), 1.96-2.07 (1H, m), 2.
24-2.33 (4H, m), 3.03 (2H, t, J = 7Hz), 4.07 (1H, quinte
t, J = 7Hz), 5.51 (2H, s), 5.65 (1H, s), 6.00 (2H, s), 7.
24 (1H, s), 7.31 (1H, br s), 7.79 (1H, d, J = 7.5Hz), 7.
94 (1H, brs), 7.95 (1H, d, J = 7.5Hz), 8.00 (1H, s) MASS (m / z): 453 (M+ +1), 85 (bp) (36) 1- (2-chlorobenzyl) -3-cyclopentanecarbonyl-2-propylindole-6-carboxamide mp: 201.5-202.5 ° C IR (KBr): 1654, 1607, 1447, 1437, 1387 cm-1 NMR (CDCl3 , δ ): 1.02 (3H, t, J = 7Hz), 1.59-1.82 (6H,
m), 1.99-2.07 (4H, m), 3.02-3.09 (2H, m), 3.79 (1H, q
uintet, J = 7Hz), 5.52 (2H, s), 6.23 (1H, d, J = 7.5Hz), 7.
05 (1H, t, J = 7.5Hz), 7.22 (1H, t, J = 7.5Hz), 7.47 (1H, d,
J = 7.5Hz), 7.63 (1H, d, J = 7.5Hz), 7.86 (1H, s), 8.04
(1H, d, J = 7.5Hz) MASS (m / z): 423 (M+ +1), 74 (bp)
【０３１５】(37) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−シクロペンタンカルボニル−
２−プロピルインドール−６−カルボキサミド mp : 236−237℃ IR (KBr) : 1662, 1506, 1477 cm-1 NMR (DMSO-d6,δ) : 0.93 (3H,t,J=7Hz), 1.40-1.50 (2
H,m), 1.61-1.68(4H,m), 1.81-1.95 (4H,m), 3.00 (2H,
t,J=7Hz), 3.73-3.82 (1H,m),5.50 (2H,s), 5.64 (1H,
s), 6.00 (2H,s), 7.24 (1H,s), 7.30 (1H,brs), 7.80
(1H,d,J=7.5Hz), 7.95 (1H,br s), 8.00 (1H,d,J=7.5H
z),8.01 (1H,s) MASS (m/z) : 467 (M++1), 85 (bp) (38) １−（２−クロロベンジル）−３−シクロヘキサ
ンカルボニル−２−プロピルインドール−６−カルボキ
サミド mp : 208−210℃ IR (KBr) : 1686, 1625, 1609, 1444, 1410 cm-1 NMR (DMSO-d6,δ) : 0.90 (3H,t,J=7Hz), 1.19-1.30 (1
H,m), 1.39-1.49(6H,m), 1.67-1.93 (5H,m), 2.99 (2H,
t,J=7Hz), 3.18-3.27 (1H,m),5.61 (2H,s), 6.19 (1H,
d,J=7.5Hz), 7.18 (1H,t,J=7.5Hz), 7.29 (1H,s), 7.32
(1H,t,J=7.5Hz), 7.58 (1H,d,J=7.5Hz), 7.80 (1H,d,J
=7.5Hz),7.90 (2H,d,J=7.5Hz), 8.00 (1H,s) MASS (m/z) : 437 (M++1), 85 (bp)(37) 1- (6-chloro-3,4-methylenedioxybenzyl) -3-cyclopentanecarbonyl-
2-propylindole-6-carboxamide mp: 236-237 ° C IR (KBr): 1662, 1506, 1477 cm-1 NMR (DMSO-d6 , δ): 0.93 (3H, t, J = 7Hz), 1.40- 1.50 (2
H, m), 1.61-1.68 (4H, m), 1.81-1.95 (4H, m), 3.00 (2H,
t, J = 7Hz), 3.73-3.82 (1H, m), 5.50 (2H, s), 5.64 (1H,
s), 6.00 (2H, s), 7.24 (1H, s), 7.30 (1H, brs), 7.80
(1H, d, J = 7.5Hz), 7.95 (1H, br s), 8.00 (1H, d, J = 7.5H
z), 8.01 (1H, s) MASS (m / z): 467 (M++ 1), 85 (bp) (38) 1- (2-chlorobenzyl) -3-cyclohexanecarbonyl-2-propylindole- 6-carboxamide mp: 208-210 ° C IR (KBr): 1686, 1625, 1609, 1444, 1410 cm-1 NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 7Hz), 1.19-1.30 (1
H, m), 1.39-1.49 (6H, m), 1.67-1.93 (5H, m), 2.99 (2H,
t, J = 7Hz), 3.18-3.27 (1H, m), 5.61 (2H, s), 6.19 (1H,
d, J = 7.5Hz), 7.18 (1H, t, J = 7.5Hz), 7.29 (1H, s), 7.32
(1H, t, J = 7.5Hz), 7.58 (1H, d, J = 7.5Hz), 7.80 (1H, d, J
= 7.5Hz), 7.90 (2H, d, J = 7.5Hz), 8.00 (1H, s) MASS (m / z): 437 (M+ +1), 85 (bp)
【０３１６】(39) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−シクロヘキサンカルボニル−
２−プロピルインドール−６−カルボキサミド mp : 209−211℃ IR (KBr) : 1623, 1611, 1506, 1391 cm-1 NMR (DMSO-d6,δ) : 0.93 (3H,t,J=7Hz), 1.20-1.28 (1
H,m), 1.39-1.51(6H,m), 1.68-1.92 (5H,m), 2.96-3.01
(2H,m), 3.19-3.27 (1H,m),5.52 (2H,s), 5.64 (1H,
s), 6.00 (2H,s), 7.24 (1H,s), 7.31 (1H,brs), 7.85
(2H,AB,J=7.5, 7.5Hz), 7.96 (1H,br s), 8.01 (1H,s) MASS (m/z) : 481 (M++1), 85 (bp) (40) １−（２−クロロベンジル）−３−（３−メチル
−２−ブテノイル）−２−プロピルインドール−６−カ
ルボキサミド mp : 187−188℃ IR (KBr) : 1680, 1648, 1614, 1598, 1446, 1384 cm-1 NMR (DMSO-d6,δ) : 0.90 (3H,t,J=7Hz), 1.49 (2H,sex
tet,J=7Hz), 2.01(3H,s), 2.10 (3H,s), 2.99 (2H,t,J=
7Hz), 5.61 (2H,s), 6.19 (1H,d,J=7.5Hz), 6.66 (1H,
s), 7.19 (1H,t,J=7.5Hz), 7.29 (1H,br s), 7.32(1H,
t,J=7.5Hz), 7.58 (1H,d,J=7.5Hz), 7.78 (1H,d,J=7.5H
z), 7.90(1H,br s), 7.97 (2H,d,J=7.5Hz) MASS (m/z) : 409 (M++1), 85 (bp)(39) 1- (6-chloro-3,4-methylenedioxybenzyl) -3-cyclohexanecarbonyl-
2-propylindole-6-carboxamide mp: 209-211 ° C IR (KBr): 1623, 1611, 1506, 1391 cm-1 NMR (DMSO-d6 , δ): 0.93 (3H, t, J = 7Hz), 1.20-1.28 (1
H, m), 1.39-1.51 (6H, m), 1.68-1.92 (5H, m), 2.96-3.01
(2H, m), 3.19-3.27 (1H, m), 5.52 (2H, s), 5.64 (1H,
s), 6.00 (2H, s), 7.24 (1H, s), 7.31 (1H, brs), 7.85
(2H, AB, J = 7.5,7.5Hz), 7.96 (1H, br s), 8.01 (1H, s) MASS (m / z): 481 (M+ +1), 85 (bp) (40) 1 -(2-chlorobenzyl) -3- (3-methyl-2-butenoyl) -2-propylindole-6-carboxamide mp: 187-188 ° C IR (KBr): 1680, 1648, 1614, 1598, 1446, 1384 cm-1 NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 7Hz), 1.49 (2H, sex
tet, J = 7Hz), 2.01 (3H, s), 2.10 (3H, s), 2.99 (2H, t, J =
7Hz), 5.61 (2H, s), 6.19 (1H, d, J = 7.5Hz), 6.66 (1H,
s), 7.19 (1H, t, J = 7.5Hz), 7.29 (1H, br s), 7.32 (1H,
t, J = 7.5Hz), 7.58 (1H, d, J = 7.5Hz), 7.78 (1H, d, J = 7.5H
z), 7.90 (1H, brs), 7.97 (2H, d, J = 7.5Hz) MASS (m / z): 409 (M+ +1), 85 (bp)
【０３１７】(41) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−（３−メチル−２−ブテノイ
ル）−２−プロピルインドール−６−カルボキサミド mp : 227−229℃ IR (KBr) : 1654, 1606, 1505, 1482, 1449, 1388 cm-1 NMR (DMSO-d6,δ) : 0.94 (3H,t,J=7Hz), 1.50 (2H,sex
tet,J=7Hz), 2.01(3H,s), 2.09 (3H,s), 3.00 (2H,t,J=
7Hz), 5.50 (2H,s), 5.67 (1H,s),6.00 (2H,s), 6.66
(1H,s), 7.25 (1H,s), 7.30 (1H,br s), 7.77 (1H,d,J=
7.5Hz), 7.91-7.99 (3H,m) MASS (m/z) : 453 (M++1), 85 (bp) (42) １−（２−クロロベンジル）−３−（３−メトキ
シブタノイル）−２−プロピルインドール−６−カルボ
キサミド mp : 155−157℃ IR (KBr) : 1656, 1610, 1447, 1437, 1389 cm-1 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.34 (3H,d,J=7
Hz), 1.63 (2H,sextet,J=7Hz), 3.01-3.09 (3H,m), 3.4
1 (3H,s), 3.47 (1H,dd,J=16,7Hz), 4.14 (1H,sextet,J
=7Hz), 5.51 (2H,s), 6.22 (1H,dd,J=7.5,1Hz), 7.05
(1H,ddd,J=7.5, 7.5, 1Hz), 7.23 (1H,ddd,J=7.5, 7.5,
1Hz), 7.46 (1H,dd,J=7.5, 1Hz), 7.62 (1H,dd,J=7.5,
1Hz), 7.76 (1H,d,J=1Hz), 8.09 (1H,d,J=7.5Hz) MASS (m/z) : 427 (M++1), 74 (bp)(41) 1- (6-chloro-3,4-methylenedioxybenzyl) -3- (3-methyl-2-butenoyl) -2-propylindole-6-carboxamide mp: 227-229 ° C IR (KBr): 1654, 1606, 1505, 1482, 1449, 1388 cm-1 NMR (DMSO-d6 , δ): 0.94 (3H, t, J = 7Hz), 1.50 (2H, sex
tet, J = 7Hz), 2.01 (3H, s), 2.09 (3H, s), 3.00 (2H, t, J =
7Hz), 5.50 (2H, s), 5.67 (1H, s), 6.00 (2H, s), 6.66
(1H, s), 7.25 (1H, s), 7.30 (1H, br s), 7.77 (1H, d, J =
7.5Hz), 7.91-7.99 (3H, m) MASS (m / z): 453 (M++ 1), 85 (bp) (42) 1- (2-chlorobenzyl) -3- (3-methoxybuta Noyl) -2-propylindole-6-carboxamide mp: 155-157 ° C IR (KBr): 1656, 1610, 1447, 1437, 1389 cm-1 NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.34 (3H, d, J = 7
Hz), 1.63 (2H, sextet, J = 7Hz), 3.01-3.09 (3H, m), 3.4
1 (3H, s), 3.47 (1H, dd, J = 16,7Hz), 4.14 (1H, sextet, J
= 7Hz), 5.51 (2H, s), 6.22 (1H, dd, J = 7.5,1Hz), 7.05
(1H, ddd, J = 7.5, 7.5, 1Hz), 7.23 (1H, ddd, J = 7.5, 7.5,
1Hz), 7.46 (1H, dd, J = 7.5, 1Hz), 7.62 (1H, dd, J = 7.5,
1Hz), 7.76 (1H, d, J = 1Hz), 8.09 (1H, d, J = 7.5Hz) MASS (m / z): 427 (M+ +1), 74 (bp)
【０３１８】(43) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−（３−メトキシブタノイル）
−２−プロピルインドール−６−カルボキサミド mp : 190−192.5℃ IR (KBr) : 1654, 1652, 1608, 1505, 1482 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.33 (3H,d,J=7
Hz), 1.62 (2H,sextet,J=7Hz), 3.00-3.09 (3H,m), 3.4
0 (3H,s), 3.45 (1H,dd,J=16,7Hz), 4.12 (1H,sextet,J
=7Hz), 5.40 (2H,s), 5.70 (1H,s), 5.90(2H,s), 6.91
(1H,s), 7.61 (1H,d,J=7.5Hz), 7.88 (1H,s), 8.08 (1
H,d,J=7.5Hz) MASS (m/z) : 471 (M++1), 74 (bp) (44) ３−アセチル−６−クロロ−１−（２−クロロベ
ンジル）インドール NMR (CDCl3,δ) : 2.49 (3H,s), 5.41 (2H,s), 6.75 (1
H,d,J=8Hz), 7.18(1H,t,J=8Hz), 7.19 (1H,t,J=8Hz),
7.2-7.33 (3H,m), 7.48 (1H,d,J=8Hz), 7.72 (1H,s),
8.33 (1H,d,J=8Hz)(43) 1- (6-chloro-3,4-methylenedioxybenzyl) -3- (3-methoxybutanoyl)
-2-Propylindole-6-carboxamide mp: 190-192.5 ° C IR (KBr): 1654, 1652, 1608, 1505, 1482 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz) , 1.33 (3H, d, J = 7
Hz), 1.62 (2H, sextet, J = 7Hz), 3.00-3.09 (3H, m), 3.4
0 (3H, s), 3.45 (1H, dd, J = 16,7Hz), 4.12 (1H, sextet, J
= 7Hz), 5.40 (2H, s), 5.70 (1H, s), 5.90 (2H, s), 6.91
(1H, s), 7.61 (1H, d, J = 7.5Hz), 7.88 (1H, s), 8.08 (1
H, d, J = 7.5Hz) MASS (m / z): 471 (M+ +1), 74 (bp) (44) 3-acetyl-6-chloro-1- (2-chlorobenzyl) indole NMR ( CDCl3 , δ): 2.49 (3H, s), 5.41 (2H, s), 6.75 (1
H, d, J = 8Hz), 7.18 (1H, t, J = 8Hz), 7.19 (1H, t, J = 8Hz),
7.2-7.33 (3H, m), 7.48 (1H, d, J = 8Hz), 7.72 (1H, s),
8.33 (1H, d, J = 8Hz)
【０３１９】製造例127 製造例55と同様にして、下記(1)〜(43)に記載の化合物
を製造した。 (1) ９−（２−クロロベンジル）−５−オキソ−５,６,
７,８−テトラヒドロカルバゾール−２−カルボン酸 NMR (CDCl3,δ) : 2.24 (2H,m), 2.63 (2H,t,J=7Hz),
2.88 (2H,t,J=7Hz),5.47 (2H,s), 6.36 (1H,d,J=8Hz),
7.09 (1H,t,J=8Hz), 7.26 (1H,t,J=8Hz), 7.47 (1H,d,J
=8Hz), 8.02 (1H,s), 8.04 (1H,d,J=8Hz), 8.37(1H,d,J
=8Hz) (2) ４−（２−クロロベンジル）−１−オキソ−１,２,
３,４−テトラヒドロシクロペンタ［ｂ］インドール−
６−カルボン酸 NMR (DMSO-d6,δ) : 2.87 (2H,m), 3.03 (2H,m), 5.64
(2H,s), 6.93 (1H,d,J=8Hz), 7.29 (1H,t,J=8Hz), 7.37
(1H,t,J=8Hz), 7.58 (1H,d,J=8Hz),7.78 (1H,d,J=8H
z), 7.83 (1H,d,J=8Hz), 8.05 (1H,s)Production Example 127 The following compounds (1) to (43) were produced in the same manner as in Production Example 55. (1) 9- (2-chlorobenzyl) -5-oxo-5,6,
7,8-tetrahydrocarbazole-2-carboxylic acid NMR (CDCl3 , δ): 2.24 (2H, m), 2.63 (2H, t, J = 7Hz),
2.88 (2H, t, J = 7Hz), 5.47 (2H, s), 6.36 (1H, d, J = 8Hz),
7.09 (1H, t, J = 8Hz), 7.26 (1H, t, J = 8Hz), 7.47 (1H, d, J
= 8Hz), 8.02 (1H, s), 8.04 (1H, d, J = 8Hz), 8.37 (1H, d, J
= 8Hz) (2) 4- (2-chlorobenzyl) -1-oxo-1,2,
3,4-tetrahydrocyclopenta [b] indole-
6-carboxylic acid NMR (DMSO-d6 , δ): 2.87 (2H, m), 3.03 (2H, m), 5.64
(2H, s), 6.93 (1H, d, J = 8Hz), 7.29 (1H, t, J = 8Hz), 7.37
(1H, t, J = 8Hz), 7.58 (1H, d, J = 8Hz), 7.78 (1H, d, J = 8H
z), 7.83 (1H, d, J = 8Hz), 8.05 (1H, s)
【０３２０】(3) １−（２−クロロベンジル）−３−イ
ソブチリル−２−プロピルインドール−７−カルボン酸 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.64 (2H,m),3.03 (2H,m), 3.56 (1H,m), 5.75 (2
H,s), 6.04 (1H,d,J=8Hz), 6.96(1H,t,J=8Hz), 7.12 (1
H,t,J=8Hz), 7.29 (1H,t,J=8Hz), 7.33 (1H,d,J=8Hz),
7.67 (1H,d,J=8Hz), 8.19 (1H,d,J=8Hz) (4) １−（２−クロロベンジル）−３−イソブチリル−
２−プロピルインドール−５−カルボン酸 NMR (DMSO-d ,δ) : 0.90 (3H,t,J=8Hz), 1.19 (6H,d,J
=8Hz), 1.62 (2H,sextet,J=8Hz), 3.02 (2H,t,J=8Hz),
3.51 (1H,septet,J=8Hz), 5.64(2H,s), 6.28 (1H,d,J=8
Hz), 7.18 (1H,t,J=8Hz), 7.32 (1H,t,J=8Hz),7.50 (1
H,d,J=8Hz), 7.56 (1H,d,J=8Hz), 7.78 (1H,d,J=8Hz),
8.58(1H,s)(3) 1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole-7-carboxylic acid NMR (CDCl3 , δ): 1.03 (3H, t, J = 7 Hz), 1.29 (6H , d, J = 7
Hz), 1.64 (2H, m), 3.03 (2H, m), 3.56 (1H, m), 5.75 (2
H, s), 6.04 (1H, d, J = 8Hz), 6.96 (1H, t, J = 8Hz), 7.12 (1
H, t, J = 8Hz), 7.29 (1H, t, J = 8Hz), 7.33 (1H, d, J = 8Hz),
7.67 (1H, d, J = 8Hz), 8.19 (1H, d, J = 8Hz) (4) 1- (2-chlorobenzyl) -3-isobutyryl-
2-propylindole-5-carboxylic acid NMR (DMSO-d, δ): 0.90 (3H, t, J = 8Hz), 1.19 (6H, d, J
= 8Hz), 1.62 (2H, sextet, J = 8Hz), 3.02 (2H, t, J = 8Hz),
3.51 (1H, septet, J = 8Hz), 5.64 (2H, s), 6.28 (1H, d, J = 8
Hz), 7.18 (1H, t, J = 8Hz), 7.32 (1H, t, J = 8Hz), 7.50 (1
H, d, J = 8Hz), 7.56 (1H, d, J = 8Hz), 7.78 (1H, d, J = 8Hz),
8.58 (1H, s)
【０３２１】(5) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−イソブチリル−２−プロピル
インドール−５−カルボン酸 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.32 (6H,d,J=7
Hz), 1.62 (2H,sextet,J=7Hz), 3.06-3.12 (2H,m), 3.6
6 (1H,septet,J=7Hz), 5.36(2H,s), 5.74 (1H,s), 5.90
(2H,s), 6.93 (1H,s), 7.23 (1H,d,J=8Hz),7.96 (1H,d
d,J=1, 8Hz), 8.76 (1H,d,J=1Hz) (6) １−（２−クロロベンジル）−２−プロピルインド
ール−４−カルボン酸 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.80 (2H,m),
2.67 (2H,t,J=7Hz),5.43 (2H,s), 6.19 (1H,d,J=8Hz),
7.03 (1H,t,J=8Hz), 7.1-7.25 (3H,m), 7.34 (1H,d,J=8
Hz), 7.41 (1H,d,J=8Hz), 7.99 (1H,d,J=8Hz)(5) 1- (6-Chloro-3,4-methylenedioxybenzyl) -3-isobutyryl-2-propylindole-5-carboxylic acid NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.32 (6H, d, J = 7
Hz), 1.62 (2H, sextet, J = 7Hz), 3.06-3.12 (2H, m), 3.6
6 (1H, septet, J = 7Hz), 5.36 (2H, s), 5.74 (1H, s), 5.90
(2H, s), 6.93 (1H, s), 7.23 (1H, d, J = 8Hz), 7.96 (1H, d
d, J = 1, 8 Hz), 8.76 (1H, d, J = 1 Hz) (6) 1- (2-chlorobenzyl) -2-propylindole-4-carboxylic acid NMR (CDCl3 , δ): 1.03 ( 3H, t, J = 7Hz), 1.80 (2H, m),
2.67 (2H, t, J = 7Hz), 5.43 (2H, s), 6.19 (1H, d, J = 8Hz),
7.03 (1H, t, J = 8Hz), 7.1-7.25 (3H, m), 7.34 (1H, d, J = 8
Hz), 7.41 (1H, d, J = 8Hz), 7.99 (1H, d, J = 8Hz)
【０３２２】(7) ９−（２−クロロベンジル）−８−オ
キソ−５,６,７,８−テトラヒドロカルバゾール−２−
カルボン酸 NMR (CDCl3,δ) : 2.28 (2H,m), 2.68 (2H,t,J=7Hz),
3.13 (2H,t,J=7Hz),5.95 (2H,s), 6.27 (1H,d,J=8Hz),
6.99 (1H,t,J=8Hz), 7.16 (1H,t,J=8Hz), 7.42 (1H,d,J
=8Hz), 7.77 (1H,d,J=8Hz), 7.87 (1H,d,J=8Hz),8.03
(1H,s) (8) ９−（６−クロロ−３,４−メチレンジオキシベン
ジル）−８−オキソ−５,６,７,８−テトラヒドロカル
バゾール−２−カルボン酸 NMR (DMSO-d6,δ) : 2.19 (2H,m), 2.63 (2H,t,J=7Hz),
3.06 (2H,t,J=7Hz),5.70 (1H,s), 5.82 (2H,s), 5.96
(2H,s), 7.16 (1H,s), 7.73 (1H,d,J=8Hz), 7.88 (1H,
d,J=8Hz), 7.98 (1H,s)(7) 9- (2-chlorobenzyl) -8-oxo-5,6,7,8-tetrahydrocarbazole-2-
Carboxylic acid NMR (CDCl3 , δ): 2.28 (2H, m), 2.68 (2H, t, J = 7Hz),
3.13 (2H, t, J = 7Hz), 5.95 (2H, s), 6.27 (1H, d, J = 8Hz),
6.99 (1H, t, J = 8Hz), 7.16 (1H, t, J = 8Hz), 7.42 (1H, d, J
= 8Hz), 7.77 (1H, d, J = 8Hz), 7.87 (1H, d, J = 8Hz), 8.03
(1H, s) (8) 9- (6-chloro-3,4-methylenedioxybenzyl) -8-oxo-5,6,7,8-tetrahydrocarbazole-2-carboxylic acid NMR (DMSO-d6 , δ): 2.19 (2H, m), 2.63 (2H, t, J = 7Hz),
3.06 (2H, t, J = 7Hz), 5.70 (1H, s), 5.82 (2H, s), 5.96
(2H, s), 7.16 (1H, s), 7.73 (1H, d, J = 8Hz), 7.88 (1H,
d, J = 8Hz), 7.98 (1H, s)
【０３２３】(9) １−（４−ブロモ−２−クロロベンジ
ル）−３−イソブチリル−２−プロピルインドール−６
−カルボン酸 mp : 234−235℃ IR (KBr) : 1677, 1648, 1418 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.54-1.64(2H,m), 3.02-3.08 (2H,m), 3.50-3.61
(1H,m), 5.44 (2H,s), 6.10(1H,t,J=8Hz), 7.18 (1H,d
d,J=8, 1Hz), 7.65 (1H,d,J=1Hz), 7.94-8.05(3H,m) MASS (m/z) : 476 (M+) (10) １−（２−クロロベンジル）−３−モルホリノア
セチル−２−プロピルインドール−６−カルボン酸 IR (KBr) : 1652, 1441, 1115 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.60 (2H,sexte
t,J=7Hz), 2.74 (4H,t,J=6.5Hz), 3.03-3.09 (2H,m),
3.86 (4H,t,J=6.5Hz), 3.93 (2H,s),5.52 (2H,s), 6.25
(1H,d,J=7.5Hz), 7.05 (1H,t,J=7.5Hz), 7.22 (1H,t,J
=7.5Hz), 7.47 (1H,d,J=7.5Hz), 7.90-8.01 (3H,m) MASS (m/z) : 455 (M+-1)(9) 1- (4-bromo-2-chlorobenzyl) -3-isobutyryl-2-propylindole-6
-Carboxylic acid mp: 234-235 ° C IR (KBr): 1677, 1648, 1418 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.54-1.64 (2H, m), 3.02-3.08 (2H, m), 3.50-3.61
(1H, m), 5.44 (2H, s), 6.10 (1H, t, J = 8Hz), 7.18 (1H, d
d, J = 8,1Hz), 7.65 (1H, d, J = 1Hz), 7.94-8.05 (3H, m) MASS (m / z): 476 (M+ ) (10) 1- (2-chlorobenzyl ) -3-morpholinoacetyl-2-propylindole-6-carboxylic acid IR (KBr): 1652, 1441, 1115 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7 Hz), 1.60 ( 2H, sexte
(t, J = 7Hz), 2.74 (4H, t, J = 6.5Hz), 3.03-3.09 (2H, m),
3.86 (4H, t, J = 6.5Hz), 3.93 (2H, s), 5.52 (2H, s), 6.25
(1H, d, J = 7.5Hz), 7.05 (1H, t, J = 7.5Hz), 7.22 (1H, t, J
= 7.5Hz), 7.47 (1H, d, J = 7.5Hz), 7.90-8.01 (3H, m) MASS (m / z): 455 (M+ -1)
【０３２４】(11) １−（２−クロロベンジル）−３−
（Ｎ,Ｎ−ジメチルカルバモイル）−２−プロピルイン
ドール−６−カルボン酸 IR (KBr) : 1704, 1596, 1219 cm-1 NMR (CDCl3,δ) : 0.93 (3H,t,J=7Hz), 1.52-1.63 (2H,
m), 2.80-2.90 (2H,m), 3.13 (6H,s), 5.48 (2H,s), 6.
30 (1H,d,J=7.5Hz), 7.04 (1H,t,J=7.5Hz), 7.20 (1H,
t,J=7.5Hz), 7.44 (1H,d,J=7.5Hz), 7.50 (1H,d,J=7.5H
z), 7.91 (1H,d,J=7.5Hz), 7.96 (1H,s) MASS (m/z) : 399 (M+-1) (12) １−（２−クロロベンジル）−３−モルホリノカ
ルボニル−２−プロピルインドール−６−カルボン酸 IR (KBr) : 3410, 1615, 1540, 1444, 1400 cm-1 NMR (DMSO-d6,δ) : 0.84 (3H,t,J=7Hz), 1.39-1.49 (2
H,m), 2.76-2.84(2H,m), 3.56 (6H,br s), 3.68 (2H,br
s), 5.52 (2H,s), 6.24 (1H,d,J=7.5Hz), 7.16 (1H,t,
J=7.5Hz), 7.29 (1H,t,J=7.5Hz), 7.40 (1H,d,J=7.5H
z), 7.54 (1H,d,J=7.5Hz), 7.79 (1H,s), 7.81 (1H,s) MASS (m/z) : 439 (M+-1), 99 (bp)(11) 1- (2-chlorobenzyl) -3-
(N, N-dimethylcarbamoyl) -2-propylindole-6-carboxylic acid IR (KBr): 1704, 1596, 1219 cm-1 NMR (CDCl3 , δ): 0.93 (3H, t, J = 7 Hz), 1.52-1.63 (2H,
m), 2.80-2.90 (2H, m), 3.13 (6H, s), 5.48 (2H, s), 6.
30 (1H, d, J = 7.5Hz), 7.04 (1H, t, J = 7.5Hz), 7.20 (1H,
t, J = 7.5Hz), 7.44 (1H, d, J = 7.5Hz), 7.50 (1H, d, J = 7.5H
z), 7.91 (1H, d, J = 7.5Hz), 7.96 (1H, s) MASS (m / z): 399 (M+ -1) (12) 1- (2-chlorobenzyl) -3-morpholino Carbonyl-2-propylindole-6-carboxylic acid IR (KBr): 3410, 1615, 1540, 1444, 1400 cm-1 NMR (DMSO-d6 , δ): 0.84 (3H, t, J = 7 Hz), 1.39 -1.49 (2
H, m), 2.76-2.84 (2H, m), 3.56 (6H, br s), 3.68 (2H, br
s), 5.52 (2H, s), 6.24 (1H, d, J = 7.5Hz), 7.16 (1H, t,
J = 7.5Hz), 7.29 (1H, t, J = 7.5Hz), 7.40 (1H, d, J = 7.5H
z), 7.54 (1H, d, J = 7.5Hz), 7.79 (1H, s), 7.81 (1H, s) MASS (m / z): 439 (M+ -1), 99 (bp)
【０３２５】(13) １−（２−クロロベンジル）−２−
プロピルインドール−３,６−ジカルボン酸 mp : 241−243℃ (分解) IR (KBr) : 1669, 1525, 1443, 1385 cm-1 NMR (DMSO-d6,δ) : 0.90 (3H,t,J=7Hz), 1.44-1.55 (2
H,m), 3.12 (2H,t,J=7Hz), 5.56 (2H,s), 6.22 (1H,d,J
=7.5Hz), 7.17 (1H,t,J=7.5Hz),7.30 (1H,t,J=7.5Hz),
7.57 (1H,d,J=7.5Hz), 7.79 (1H,s), 8.06 (1H,d,J=7.5
Hz) MASS (m/z) : 370 (M+-1), 99 (bp) (14) １−（２−クロロベンジル）−２−エチル−３−
ホルミルインドール−６−カルボン酸 mp : 241−242℃ (分解) IR (KBr) : 1675, 1650, 1295 cm-1 NMR (CDCl3,δ) : 1.29 (3H,t,J=7Hz), 3.09 (2H,q,J=7
Hz), 5.52 (2H,s),6.30 (1H,d,J=7.5Hz), 7.08 (1H,t,J
=7.5Hz), 7.25 (1H,t,J=7.5Hz),7.49 (1H,d,J=7.5Hz),
7.97 (1H,s), 8.03 (1H,d,J=7.5Hz), 8.35 (1H,d,J=7.5
Hz), 10.25 (1H,s) MASS (m/z) : 340 (M+-1)(13) 1- (2-chlorobenzyl) -2-
Propylindole-3,6-dicarboxylic acid mp: 241-243 ° C (decomposition) IR (KBr): 1669, 1525, 1443, 1385 cm-1 NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 7Hz), 1.44-1.55 (2
H, m), 3.12 (2H, t, J = 7Hz), 5.56 (2H, s), 6.22 (1H, d, J
= 7.5Hz), 7.17 (1H, t, J = 7.5Hz), 7.30 (1H, t, J = 7.5Hz),
7.57 (1H, d, J = 7.5Hz), 7.79 (1H, s), 8.06 (1H, d, J = 7.5
Hz) MASS (m / z): 370 (M+ -1), 99 (bp) (14) 1- (2-chlorobenzyl) -2-ethyl-3-
Formyl indole-6-carboxylic acid mp: 241-242 ° C (decomposition) IR (KBr): 1675, 1650, 1295 cm-1 NMR (CDCl3 , δ): 1.29 (3H, t, J = 7Hz), 3.09 ( 2H, q, J = 7
Hz), 5.52 (2H, s), 6.30 (1H, d, J = 7.5Hz), 7.08 (1H, t, J
= 7.5Hz), 7.25 (1H, t, J = 7.5Hz), 7.49 (1H, d, J = 7.5Hz),
7.97 (1H, s), 8.03 (1H, d, J = 7.5Hz), 8.35 (1H, d, J = 7.5
Hz), 10.25 (1H, s) MASS (m / z): 340 (M+ -1)
【０３２６】(15) １−（２−クロロベンジル）−３−
ホルミルインドール−６−カルボン酸 NMR (DMSO-d6,δ) : 5.73 (2H,s), 6.96 (1H,d,J=8Hz),
7.23-7.4 (2H,m),7.56 (1H,d,J=8Hz), 7.89 (1H,d,J=8
Hz), 8.15 (1H,s), 8.21 (1H,s),8.54 (1H,s), 10.0 (1
H,s) (16) ３−アセチル−１−（２−クロロベンジル）−２
−メチルインドール−６−カルボン酸 NMR (CDCl3,δ) : 2.71 (3H,s), 2.76 (3H,s), 5.50 (2
H,s), 6.22 (1H,d,J=8Hz), 7.05 (1H,t,J=8Hz), 7.22
(1H,t,J=8Hz), 7.47 (1H,d,J=8Hz),7.95-8.15 (3H,m),
8.08 (1H,d,J=8Hz)(15) 1- (2-chlorobenzyl) -3-
Formyl indole-6-carboxylic acidNMR (DMSO-d 6, δ ): 5.73 (2H, s), 6.96 (1H, d, J = 8Hz),
7.23-7.4 (2H, m), 7.56 (1H, d, J = 8Hz), 7.89 (1H, d, J = 8
Hz), 8.15 (1H, s), 8.21 (1H, s), 8.54 (1H, s), 10.0 (1
H, s) (16) 3-acetyl-1- (2-chlorobenzyl) -2
- methylindole-6-carboxylic acidNMR (CDCl 3, δ): 2.71 (3H, s), 2.76 (3H, s), 5.50 (2
H, s), 6.22 (1H, d, J = 8Hz), 7.05 (1H, t, J = 8Hz), 7.22
(1H, t, J = 8Hz), 7.47 (1H, d, J = 8Hz), 7.95-8.15 (3H, m),
8.08 (1H, d, J = 8Hz)
【０３２７】(17) １−（２−クロロベンジル）−２−
メチル−３−プロピオニルインドール−６−カルボン酸 NMR (DMSO-d6,δ) : 1.14 (3H,t,J=7Hz), 2.69 (3H,s),
3.04 (2H,q,J=7Hz),5.67 (2H,s), 6.24 (1H,d,J=8Hz),
7.18 (1H,d,J=8Hz), 7.22 (1H,t,J=8Hz), 7.58 (1H,d,
J=8Hz), 7.83 (1H,d,J=8Hz), 7.99 (1H,s), 8.16(1H,d,
J=8Hz) (18) １−（２−クロロベンゾ［ｂ］チオフェン−３−
イルメチル）−３−イソブチリル−２−メチルインドー
ル−６−カルボン酸 NMR (CDCl3,δ) : 1.25 (6H,d,J=7Hz), 2.71 (3H,s),
3.50 (1H,m), 5.61(2H,s), 6.99 (1H,d,J=8Hz), 7.12
(1H,t,J=8Hz), 7.28 (1H,t,J=8Hz),7.68 (1H,d,J=8Hz),
7.95-8.02 (2H,m), 8.23 (1H,s)(17) 1- (2-chlorobenzyl) -2-
Methyl-3-propionyl-indole-6-carboxylic acidNMR (DMSO-d 6, δ ): 1.14 (3H, t, J = 7Hz), 2.69 (3H, s),
3.04 (2H, q, J = 7Hz), 5.67 (2H, s), 6.24 (1H, d, J = 8Hz),
7.18 (1H, d, J = 8Hz), 7.22 (1H, t, J = 8Hz), 7.58 (1H, d,
J = 8Hz), 7.83 (1H, d, J = 8Hz), 7.99 (1H, s), 8.16 (1H, d,
J = 8 Hz) (18) 1- (2-chlorobenzo [b] thiophen-3-
Ylmethyl) -3-isobutyryl-2-methylindole-6-carboxylic acid NMR (CDCl3 , δ): 1.25 (6H, d, J = 7 Hz), 2.71 (3H, s),
3.50 (1H, m), 5.61 (2H, s), 6.99 (1H, d, J = 8Hz), 7.12
(1H, t, J = 8Hz), 7.28 (1H, t, J = 8Hz), 7.68 (1H, d, J = 8Hz),
7.95-8.02 (2H, m), 8.23 (1H, s)
【０３２８】(19) １−（ベンゾチアゾール−２−イル
メチル）−２−エチル−３−イソブチリルインドール−
６−カルボン酸 NMR (CDCl3,δ) : 1.28 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 3.24 (2H,q,J=7Hz), 3.58 (1H,m), 5.86 (2H,s),
7.39 (1H,t,J=8Hz), 7.52 (1H,t,J=8Hz), 7.87 (1H,d,J
=8Hz), 7.9-8.06 (3H,m), 8.20 (1H,s) (20) １−（ベンゾ［ｂ］チオフェン−５−イルメチ
ル）−３−イソブチリル−２−プロピルインドール−６
−カルボン酸 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.32 (6H,d,J=7
Hz), 1.63 (2H,m),3.14 (2H,m), 3.57 (1H,m), 5.58 (2
H,s), 7.04 (1H,d,J=8Hz), 7.19(1H,d,J=6Hz), 7.31 (1
H,s), 7.43 (1H,d,J=6Hz), 7.81 (1H,d,J=8Hz),7.9-8.0
2 (2H,m), 8.08 (1H,s)(19) 1- (benzothiazol-2-ylmethyl) -2-ethyl-3-isobutyrylindole-
6-carboxylic acid NMR (CDCl3 , δ): 1.28 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 3.24 (2H, q, J = 7Hz), 3.58 (1H, m), 5.86 (2H, s),
7.39 (1H, t, J = 8Hz), 7.52 (1H, t, J = 8Hz), 7.87 (1H, d, J
= 8Hz), 7.9-8.06 (3H, m), 8.20 (1H, s) (20) 1- (Benzo [b] thiophen-5-ylmethyl) -3-isobutyryl-2-propylindole-6
- carboxylic acidNMR (CDCl 3, δ): 1.02 (3H, t, J = 7Hz), 1.32 (6H, d, J = 7
Hz), 1.63 (2H, m), 3.14 (2H, m), 3.57 (1H, m), 5.58 (2
H, s), 7.04 (1H, d, J = 8Hz), 7.19 (1H, d, J = 6Hz), 7.31 (1
H, s), 7.43 (1H, d, J = 6Hz), 7.81 (1H, d, J = 8Hz), 7.9-8.0
2 (2H, m), 8.08 (1H, s)
【０３２９】(21) １−（２,４−ジクロロベンジル）−
３−イソブチリル−２−プロピルインドール−６−カル
ボン酸 NMR (DMSO-d6,δ) : 0.92 (3H,t,J=7Hz), 1.18 (6H,d,J
=7Hz), 1.46 (2H,sextet,J=7Hz), 3.02-3.07 (2H,m),
3.54 (2H,septet,J=7Hz), 5.68 (2H,s), 6.27 (1H,d,J=
8Hz), 7.28 (1H,dd,J=2, 8Hz), 7.76 (1H,d,J=2Hz),7.8
4 (1H,d,J=8Hz), 7.96 (1H,s), 8.01 (1H,d,J=8Hz) (22) ３−イソブチリル−２−プロピル−１−（３−ピ
リジルメチル）インドール−６−カルボン酸 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.63 (2H,sextet,J=7Hz), 3.15 (2H,t,J=7Hz), 3.
57 (2H,septet,J=7Hz), 5.51(2H,s), 7.19-7.28 (2H,
m), 7.95-8.01 (2H,m), 8.04 (1H,s), 8.52-8.56(2H,m)(21) 1- (2,4-dichlorobenzyl)-
3-isobutyryl-2-propylindole-6-carboxylic acid NMR (DMSO-d6 , δ): 0.92 (3H, t, J = 7Hz), 1.18 (6H, d, J
= 7Hz), 1.46 (2H, sextet, J = 7Hz), 3.02-3.07 (2H, m),
3.54 (2H, septet, J = 7Hz), 5.68 (2H, s), 6.27 (1H, d, J =
8Hz), 7.28 (1H, dd, J = 2,8Hz), 7.76 (1H, d, J = 2Hz), 7.8
4 (1H, d, J = 8Hz), 7.96 (1H, s), 8.01 (1H, d, J = 8Hz) (22) 3-Isobutyryl-2-propyl-1- (3-pyridylmethyl) indole-6 - carboxylic acidNMR (CDCl 3, δ): 1.04 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.63 (2H, sextet, J = 7Hz), 3.15 (2H, t, J = 7Hz), 3.
57 (2H, septet, J = 7Hz), 5.51 (2H, s), 7.19-7.28 (2H,
m), 7.95-8.01 (2H, m), 8.04 (1H, s), 8.52-8.56 (2H, m)
【０３３０】(23) ３−イソブチリル−２−プロピル−
１−（１−ナフチルメチル）インドール−６−カルボン
酸 NMR (DMSO-d6,δ) : 0.86 (3H,t,J=7Hz), 1.22 (6H,d,J
=7Hz), 1.52 (2H,sextet,J=7Hz), 3.05-3.10 (2H,m),
3.60 (1H,septet,J=7Hz), 6.15(1H,d,J=8Hz), 6.17 (2
H,s), 7.28 (1H,t,J=8Hz), 7.64 (1H,t,J=8Hz),7.72 (1
H,t,J=8Hz), 7.84 (2H,d,J=8Hz), 7.92 (1H,s), 8.12
(1H,d,J=8Hz), 8.15 (1H,d,J=8Hz), 8.36 (1H,d,J=8Hz) (24) ３−イソブチリル−２−プロピル−１−（２−ナ
フチルメチル）インドール−６−カルボン酸 NMR (DMSO-d6,δ) : 0.92 (3H,t,J=7Hz), 1.19 (6H,d,J
=7Hz), 1.48 (2H,sextet,J=7Hz), 3.14-3.18 (2H,m),
3.57 (1H,septet,J=7Hz), 5.81(2H,s), 7.20 (1H,d,J=8
Hz), 7.45-7.52 (3H,m), 7.76-7.90 (4H,m),8.02 (1H,
d,J=8Hz), 8.08 (1H,s)(23) 3-isobutyryl-2-propyl-
1- (1-Naphthylmethyl) indole-6-carboxylic acid NMR (DMSO-d6 , δ): 0.86 (3H, t, J = 7 Hz), 1.22 (6H, d, J
= 7Hz), 1.52 (2H, sextet, J = 7Hz), 3.05-3.10 (2H, m),
3.60 (1H, septet, J = 7Hz), 6.15 (1H, d, J = 8Hz), 6.17 (2
H, s), 7.28 (1H, t, J = 8Hz), 7.64 (1H, t, J = 8Hz), 7.72 (1
(H, t, J = 8Hz), 7.84 (2H, d, J = 8Hz), 7.92 (1H, s), 8.12
(1H, d, J = 8Hz), 8.15 (1H, d, J = 8Hz), 8.36 (1H, d, J = 8Hz) (24) 3-isobutyryl-2-propyl-1- (2-naphthylmethyl) indole-6-carboxylic acidNMR (DMSO-d 6, δ ): 0.92 (3H, t, J = 7Hz), 1.19 (6H, d, J
= 7Hz), 1.48 (2H, sextet, J = 7Hz), 3.14-3.18 (2H, m),
3.57 (1H, septet, J = 7Hz), 5.81 (2H, s), 7.20 (1H, d, J = 8
Hz), 7.45-7.52 (3H, m), 7.76-7.90 (4H, m), 8.02 (1H,
d, J = 8Hz), 8.08 (1H, s)
【０３３１】(25) １−アリル−３−イソブチリル−２
−プロピルインドール−６−カルボン酸 NMR (CDCl3,δ) : 1.08 (3H,t,J=7Hz), 1.28 (6H,d,J=7
Hz), 1.69 (2H,m),3.13 (2H,m), 3.56 (1H,m), 4.88 (2
H,m), 4.90 (1H,m), 5.23 (1H,m),5.98 (1H,m), 7.94
(1H,d,J=8Hz), 8.02 (1H,d,J=8Hz), 8.13 (1H,s) (26) １−（２−クロロベンジル）−３−イソブチリル
−２−（１−プロペニル）インドール−６−カルボン酸 NMR (CDCl3,δ) : 1.26 (6H,d,J=7Hz), 1.93 (3H,d,J=7
Hz), 3.51 (1H,m),5.50 (2H,s), 5.92 (1H,m), 6.44 (1
H,d,J=8Hz), 6.74 (1H,d,J=16Hz),7.09 (1H,t,J=8Hz),
7.23 (1H,t,J=8Hz), 7.48 (1H,d,J=8Hz), 7.92(1H,s),
8.02 (1H,d,J=8Hz), 8.21 (1H,d,J=8Hz)(25) 1-allyl-3-isobutyryl-2
- propyl indole-6-carboxylic acidNMR (CDCl 3, δ): 1.08 (3H, t, J = 7Hz), 1.28 (6H, d, J = 7
Hz), 1.69 (2H, m), 3.13 (2H, m), 3.56 (1H, m), 4.88 (2
H, m), 4.90 (1H, m), 5.23 (1H, m), 5.98 (1H, m), 7.94
(1H, d, J = 8Hz), 8.02 (1H, d, J = 8Hz), 8.13 (1H, s) (26) 1- (2-chlorobenzyl) -3-isobutyryl-2- (1-propenyl) Indole-6-carboxylic acid NMR (CDCl3 , δ): 1.26 (6H, d, J = 7Hz), 1.93 (3H, d, J = 7
Hz), 3.51 (1H, m), 5.50 (2H, s), 5.92 (1H, m), 6.44 (1
(H, d, J = 8Hz), 6.74 (1H, d, J = 16Hz), 7.09 (1H, t, J = 8Hz),
7.23 (1H, t, J = 8Hz), 7.48 (1H, d, J = 8Hz), 7.92 (1H, s),
8.02 (1H, d, J = 8Hz), 8.21 (1H, d, J = 8Hz)
【０３３２】(27) １−（２−クロロベンジル）−２−
（１−ヒドロキシプロピル）−３−イソブチリルインド
ール−６−カルボン酸 NMR (CDCl3,δ) : 0.92 (3H,t,J=7Hz), 1.29 (3H,d,J=7
Hz), 1.36 (3H,d,J=7Hz), 1.52 (1H,m), 1.88 (1H,m),
3.70 (1H,m), 4.73 (1H,m), 5.51(1H,d,J=17Hz), 5.69
(1H,d,J=17Hz), 6.44 (1H,d,J=8Hz), 7.09 (1H,t,J=8H
z), 7.23 (1H,t,J=8Hz), 7.45 (1H,d,J=8Hz), 7.9-8.1
(3H,m) (28) １−（２−クロロベンジル）−３−（３,３−ジメ
チルブタノイル）インドール−６−カルボン酸 NMR (CDCl3,δ) : 1.08 (9H,s), 2.70 (2H,s), 5.52 (2
H,s), 6.77 (1H,d,J=8Hz), 7.17 (1H,t,J=8Hz), 7.28
(1H,t,J=8Hz), 7.47 (1H,d,J=8Hz),7.86 (1H,s), 8.03
(1H,d,J=8Hz), 8.12 (1H,s), 8.53 (1H,d,J=8Hz)(27) 1- (2-chlorobenzyl) -2-
(1-hydroxypropyl) -3-isobutyryl-indole-6-carboxylic acidNMR (CDCl 3, δ): 0.92 (3H, t, J = 7Hz), 1.29 (3H, d, J = 7
Hz), 1.36 (3H, d, J = 7Hz), 1.52 (1H, m), 1.88 (1H, m),
3.70 (1H, m), 4.73 (1H, m), 5.51 (1H, d, J = 17Hz), 5.69
(1H, d, J = 17Hz), 6.44 (1H, d, J = 8Hz), 7.09 (1H, t, J = 8H)
z), 7.23 (1H, t, J = 8Hz), 7.45 (1H, d, J = 8Hz), 7.9-8.1
(3H, m) (28) 1- (2-chlorobenzyl) -3- (3,3-dimethylbutanoyl) indole-6-carboxylic acid NMR (CDCl3 , δ): 1.08 (9H, s), 2.70 (2H, s), 5.52 (2
H, s), 6.77 (1H, d, J = 8Hz), 7.17 (1H, t, J = 8Hz), 7.28
(1H, t, J = 8Hz), 7.47 (1H, d, J = 8Hz), 7.86 (1H, s), 8.03
(1H, d, J = 8Hz), 8.12 (1H, s), 8.53 (1H, d, J = 8Hz)
【０３３３】(29) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−メトキシアセチル−２−プロ
ピルインドール−６−カルボン酸 NMR (CDCl3,δ) : 0.96 (3H,t,J=7Hz), 1.45-1.58 (2H,
m), 3.10 (2H,t,J=7Hz), 3.40 (3H,s), 4.69 (2H,s),
5.55 (2H,s), 5.76 (1H,s), 5.98(2H,s), 7.23 (1H,s),
7.82 (1H,d,J=8Hz), 7.94 (1H,s), 7.96 (1H,d,J=8Hz) (30) １−（２−クロロベンジル）−３−エトキシアセ
チル−２−プロピルインドール−６−カルボン酸 NMR (DMSO-d6,δ) : 0.94 (3H,t,J=7Hz), 1.17 (3H,t,J
=7Hz), 1.48 (2H,sextet,J=7Hz), 3.08 (3H,t,J=7Hz),
3.62 (2H,q,J=7Hz), 4.74 (2H,s),5.68 (2H,s), 6.28
(1H,d,J=8Hz), 7.18 (1H,t,J=8Hz), 7.32 (1H,t,J=8H
z), 7.56 (1H,d,J=8Hz), 7.82 (1H,d,J=8Hz), 7.96 (1
H,s), 7.98(1H,d,J=8Hz)(29) 1- (6-Chloro-3,4-methylenedioxybenzyl) -3-methoxyacetyl-2-propylindole-6-carboxylic acid NMR (CDCl3 , δ): 0.96 (3H, t , J = 7Hz), 1.45-1.58 (2H,
m), 3.10 (2H, t, J = 7Hz), 3.40 (3H, s), 4.69 (2H, s),
5.55 (2H, s), 5.76 (1H, s), 5.98 (2H, s), 7.23 (1H, s),
7.82 (1H, d, J = 8Hz), 7.94 (1H, s), 7.96 (1H, d, J = 8Hz) (30) 1- (2-chlorobenzyl) -3-ethoxyacetyl-2-propylindole- 6-carboxylic acid NMR (DMSO-d6 , δ): 0.94 (3H, t, J = 7Hz), 1.17 (3H, t, J
= 7Hz), 1.48 (2H, sextet, J = 7Hz), 3.08 (3H, t, J = 7Hz),
3.62 (2H, q, J = 7Hz), 4.74 (2H, s), 5.68 (2H, s), 6.28
(1H, d, J = 8Hz), 7.18 (1H, t, J = 8Hz), 7.32 (1H, t, J = 8H)
z), 7.56 (1H, d, J = 8Hz), 7.82 (1H, d, J = 8Hz), 7.96 (1
H, s), 7.98 (1H, d, J = 8Hz)
【０３３４】(31) １−（２−クロロベンジル）−３−
イソブチリル−２−プロピルインドール−６−イル酢酸 IR (KBr) : 1715, 1650 cm-1 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.54-1.66 (2H,m), 3.00-3.08 (2H,m), 3.50-3.62
(1H,m), 3.71 (2H,s), 5.47 (2H,s),6.30 (1H,d,J=7.5
Hz), 7.01-7.08 (2H,m), 7.19-7.25 (2H,m), 7.45 (1H,
d,J=7.5Hz), 7.89 (1H,d,J=7.5Hz) MASS (m/z) : 412 (M++1), 74 (bp) (32) １−（６−クロロ−３,４−メチレンジオキシベン
ジル）−３−イソブチリル−２−プロピルインドール−
６−イル酢酸 mp : 81−83℃ IR (KBr) : 1715, 1650 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.54-1.67 (2H,m), 3.01-3.07 (2H,m), 3.51-3.60
(1H,m), 3.75 (2H,s), 5.33 (2H,s),5.79 (1H,s), 5.8
9 (2H,s), 6.91 (1H,s), 7.12 (1H,s), 7.21 (1H,d,J=
7.5Hz), 7.89 (1H,d,J=7.5Hz) MASS (m/z) : 456 (M++1), 74 (bp)(31) 1- (2-chlorobenzyl) -3-
Isobutyryl-2-propylindol-6-ylacetic acid IR (KBr): 1715, 1650 cm-1 NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.54-1.66 (2H, m), 3.00-3.08 (2H, m), 3.50-3.62
(1H, m), 3.71 (2H, s), 5.47 (2H, s), 6.30 (1H, d, J = 7.5
Hz), 7.01-7.08 (2H, m), 7.19-7.25 (2H, m), 7.45 (1H,
d, J = 7.5Hz), 7.89 (1H, d, J = 7.5Hz) MASS (m / z): 412 (M+ +1), 74 (bp) (32) 1- (6-chloro-3, 4-methylenedioxybenzyl) -3-isobutyryl-2-propylindole-
6-ylacetic acid mp: 81-83 ° C IR (KBr): 1715, 1650 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.29 (6H, d, J = 7
Hz), 1.54-1.67 (2H, m), 3.01-3.07 (2H, m), 3.51-3.60
(1H, m), 3.75 (2H, s), 5.33 (2H, s), 5.79 (1H, s), 5.8
9 (2H, s), 6.91 (1H, s), 7.12 (1H, s), 7.21 (1H, d, J =
7.5Hz), 7.89 (1H, d, J = 7.5Hz) MASS (m / z): 456 (M+ +1), 74 (bp)
【０３３５】(33) １−（２−クロロベンジル）−２−
プロピルインドール−６−カルボン酸 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.74 (2H,m),
2.61 (2H,t,J=7Hz),5.42 (2H,s), 6.19 (1H,d,J=8Hz),
6.46 (1H,s), 7.02 (1H,t,J=8Hz),7.18 (1H,t,J=8Hz),
7.43 (1H,d,J=8Hz), 7.61 (1H,d,J=8Hz), 7.85(1H,d,J=
8Hz), 7.95 (1H,s) (34) １−（２−ブロモベンジル）−２−プロピルイン
ドール−６−カルボン酸 NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.73 (2H,m),
2.61 (2H,t,J=7Hz),5.37 (2H,s), 6.12 (1H,d,J=8Hz),
6.46 (1H,s), 7.0-7.18 (2H,m),7.61 (1H,d,J=8Hz), 7.
85 (1H,d,J=8Hz), 7.96 (1H,s)(33) 1- (2-chlorobenzyl) -2-
Propyl indole-6-carboxylic acidNMR (CDCl 3, δ): 1.02 (3H, t, J = 7Hz), 1.74 (2H, m),
2.61 (2H, t, J = 7Hz), 5.42 (2H, s), 6.19 (1H, d, J = 8Hz),
6.46 (1H, s), 7.02 (1H, t, J = 8Hz), 7.18 (1H, t, J = 8Hz),
7.43 (1H, d, J = 8Hz), 7.61 (1H, d, J = 8Hz), 7.85 (1H, d, J =
8 Hz), 7.95 (1H, s) (34) 1- (2-bromobenzyl) -2-propylindole-6-carboxylic acid NMR (CDCl3 , δ): 1.00 (3H, t, J = 7 Hz), 1.73 (2H, m),
2.61 (2H, t, J = 7Hz), 5.37 (2H, s), 6.12 (1H, d, J = 8Hz),
6.46 (1H, s), 7.0-7.18 (2H, m), 7.61 (1H, d, J = 8Hz), 7.
85 (1H, d, J = 8Hz), 7.96 (1H, s)
【０３３６】(35) ２−アセチル−１−（２−クロロベ
ンジル）−３−メチルインドール−６−カルボン酸 NMR (DMSO-d6,δ) : 2.62 (3H,s), 2.69 (3H,s), 5.82
(2H,s), 6.10 (1H,d,J=8Hz), 7.09 (1H,t,J=8Hz), 7.24
(1H,t,J=8Hz), 7.51 (1H,d,J=8Hz),7.72 (1H,d,J=8H
z), 7.93 (1H,d,J=8Hz), 7.96 (1H,s) (36) ２−クロロ−１−（２−クロロベンジル）−３−
エチルインドール−６−カルボン酸 NMR (CDCl3,δ) : 1.30 (3H,t,J=7Hz), 2.84 (2H,q,J=7
Hz), 5.50 (2H,s),6.29 (1H,d,J=8Hz), 7.06 (1H,t,J=8
Hz), 7.19 (1H,t,J=8Hz), 7.43 (1H,d,J=8Hz), 7.63 (1
H,d,J=8Hz), 7.88 (1H,d,J=8Hz), 7.93 (1H,s)(35) 2-acetyl-1- (2-chlorobenzyl) -3-methylindole-6-carboxylic acid NMR (DMSO-d6 , δ): 2.62 (3H, s), 2.69 (3H, s ), 5.82
(2H, s), 6.10 (1H, d, J = 8Hz), 7.09 (1H, t, J = 8Hz), 7.24
(1H, t, J = 8Hz), 7.51 (1H, d, J = 8Hz), 7.72 (1H, d, J = 8H)
z), 7.93 (1H, d, J = 8Hz), 7.96 (1H, s) (36) 2-chloro-1- (2-chlorobenzyl) -3-
Ethyl indole-6-carboxylic acidNMR (CDCl 3, δ): 1.30 (3H, t, J = 7Hz), 2.84 (2H, q, J = 7
Hz), 5.50 (2H, s), 6.29 (1H, d, J = 8Hz), 7.06 (1H, t, J = 8
Hz), 7.19 (1H, t, J = 8Hz), 7.43 (1H, d, J = 8Hz), 7.63 (1
(H, d, J = 8Hz), 7.88 (1H, d, J = 8Hz), 7.93 (1H, s)
【０３３７】(37) １−（２−クロロベンジル）−２−
プロピオニル−３−プロピルインドール−６−カルボン
酸 NMR (CDCl3,δ) : 1.06 (3H,t,J=7Hz), 1.14 (3H,t,J=7
Hz), 1.76 (2H,m),2.94 (2H,q,J=7Hz), 3.09 (2H,m),
5.72 (2H,s), 6.27 (1H,d,J=8Hz),6.99 (1H,t,J=8Hz),
7.14 (1H,t,J=8Hz), 7.39 (1H,d,J=8Hz), 7.78(1H,d,J=
8Hz), 7.87 (1H,d,J=8Hz), 8.02 (1H,s) (38) １−（２−クロロベンジル）−２−イソブチリル
−３−プロピルインドール−６−カルボン酸 NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.11 (6H,d,J=7
Hz), 1.76 (2H,m),3.03 (2H,m), 3.34 (1H,m), 5.64 (2
H,s), 6.30 (1H,d,J=8Hz), 7.01(1H,t,J=8Hz), 7.14 (1
H,t,J=8Hz), 7.39 (1H,d,J=8Hz), 7.78 (1H,d,J=8Hz),
7.88 (1H,d,J=8Hz), 8.02 (1H,s)(37) 1- (2-chlorobenzyl) -2-
Propionyl-3-propyl indole-6-carboxylic acidNMR (CDCl 3, δ): 1.06 (3H, t, J = 7Hz), 1.14 (3H, t, J = 7
Hz), 1.76 (2H, m), 2.94 (2H, q, J = 7Hz), 3.09 (2H, m),
5.72 (2H, s), 6.27 (1H, d, J = 8Hz), 6.99 (1H, t, J = 8Hz),
7.14 (1H, t, J = 8Hz), 7.39 (1H, d, J = 8Hz), 7.78 (1H, d, J =
8Hz), 7.87 (1H, d, J = 8Hz), 8.02 (1H, s) (38) 1- (2-chlorobenzyl) -2-isobutyryl-3-propylindole-6-carboxylic acid NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.11 (6H, d, J = 7
Hz), 1.76 (2H, m), 3.03 (2H, m), 3.34 (1H, m), 5.64 (2
H, s), 6.30 (1H, d, J = 8Hz), 7.01 (1H, t, J = 8Hz), 7.14 (1
H, t, J = 8Hz), 7.39 (1H, d, J = 8Hz), 7.78 (1H, d, J = 8Hz),
7.88 (1H, d, J = 8Hz), 8.02 (1H, s)
【０３３８】(39) １−（２−クロロベンジル）−３−
（３−オキソ−１−ブテニル）インドール−６−カルボ
ン酸 NMR (DMSO-d6,δ) : 2.32 (3H,s), 5.67 (2H,s), 6.76
(1H,d,J=15Hz), 6.86(1H,d,J=8Hz), 7.28 (1H,t,J=8H
z), 7.37 (1H,t,J=8Hz), 7.54 (1H,d,J=8Hz), 7.79 (1
H,d,J=8Hz), 7.83 (1H,d,J=15Hz), 8.08 (1H,d,J=8Hz),
8.11 (1H,s), 8.21 (1H,s) (40) ４−（２−クロロベンジル）−３−オキソ−１,
２,３,４−テトラヒドロシクロペンタ［ｂ］インドール
−６−カルボン酸 NMR (CDCl3,δ) : 3.07 (2H,m), 3.17 (2H,m), 5.72 (2
H,s), 6.58 (1H,d,J=8Hz), 7.06 (1H,t,J=8Hz), 7.18
(1H,t,J=8Hz), 7.40 (1H,d,J=8Hz),7.78 (1H,d,J=8Hz),
7.89 (1H,d,J=8Hz), 8.09 (1H,s)(39) 1- (2-chlorobenzyl) -3-
(3-oxo-1-butenyl) indole-6-carboxylic acid NMR (DMSO-d6 , δ): 2.32 (3H, s), 5.67 (2H, s), 6.76
(1H, d, J = 15Hz), 6.86 (1H, d, J = 8Hz), 7.28 (1H, t, J = 8H
z), 7.37 (1H, t, J = 8Hz), 7.54 (1H, d, J = 8Hz), 7.79 (1
H, d, J = 8Hz), 7.83 (1H, d, J = 15Hz), 8.08 (1H, d, J = 8Hz),
8.11 (1H, s), 8.21 (1H, s) (40) 4- (2-chlorobenzyl) -3-oxo-1,
2,3,4-tetrahydrocyclopenta [b] indole-6-carboxylic acid NMR (CDCl3 , δ): 3.07 (2H, m), 3.17 (2H, m), 5.72 (2
H, s), 6.58 (1H, d, J = 8Hz), 7.06 (1H, t, J = 8Hz), 7.18
(1H, t, J = 8Hz), 7.40 (1H, d, J = 8Hz), 7.78 (1H, d, J = 8Hz),
7.89 (1H, d, J = 8Hz), 8.09 (1H, s)
【０３３９】(41) ４−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−オキソ−１,２,３,４−テト
ラヒドロシクロペンタ［ｂ］インドール−６−カルボン
酸 NMR (CDCl3,δ) : 3.07 (2H,m), 3.16 (2H,m), 5.61 (2
H,s), 5.88 (2H,s),6.10 (1H,s), 6.88 (1H,s), 7.78
(1H,d,J=8Hz), 7.88 (1H,d,J=8Hz),8.12 (1H,s) (42) １−（２−クロロベンジル）−３−ニトロ−２−
プロピルインドール−６−カルボン酸 NMR (DMSO-d6,δ) : 0.95 (3H,t,J=7Hz), 1.55 (2H,sex
tet,J=7Hz), 3.18-3.22 (2H,m), 5.78 (2H,s), 6.52 (1
H,d,J=8Hz), 7.22 (1H,t,J=8Hz),7.33 (1H,t,J=8Hz),
7.58 (1H,d,J=8Hz), 7.97 (1H,d,J=8Hz), 8.08(1H,s),
8.27 (1H,d,J=8Hz)(41) 4- (6-Chloro-3,4-methylenedioxybenzyl) -3-oxo-1,2,3,4-tetrahydrocyclopenta [b] indole-6-carboxylic acid NMR (CDCl3 , δ): 3.07 (2H, m), 3.16 (2H, m), 5.61 (2
H, s), 5.88 (2H, s), 6.10 (1H, s), 6.88 (1H, s), 7.78
(1H, d, J = 8Hz), 7.88 (1H, d, J = 8Hz), 8.12 (1H, s) (42) 1- (2-chlorobenzyl) -3-nitro-2-
Propyl indole-6-carboxylic acidNMR (DMSO-d 6, δ ): 0.95 (3H, t, J = 7Hz), 1.55 (2H, sex
tet, J = 7Hz), 3.18-3.22 (2H, m), 5.78 (2H, s), 6.52 (1
H, d, J = 8Hz), 7.22 (1H, t, J = 8Hz), 7.33 (1H, t, J = 8Hz),
7.58 (1H, d, J = 8Hz), 7.97 (1H, d, J = 8Hz), 8.08 (1H, s),
8.27 (1H, d, J = 8Hz)
【０３４０】(43) １−（２−クロロ−４−カルボキシ
ベンジル）−３−イソブチリル−２−プロピルインドー
ル−６−カルボキサミド NMR (DMSO-d6,δ) : 0.90 (3H,t,J=7Hz), 1.18 (6H,d,J
=7Hz), 1.46 (2H,sextet,J=7Hz), 3.00-3.05 (2H,m),
3.55 (1H,septet,J=7Hz), 5.68(2H,s), 6.33 (1H,d,J=8
Hz), 7.30 (1H,s), 7.72 (1H,dd,J=2, 8Hz),7.92 (1H,
s), 7.95-7.99 (2H,m), 8.03 (1H,d,J=8Hz)(43) 1- (2-chloro-4-carboxybenzyl) -3-isobutyryl-2-propylindole-6-carboxamide NMR (DMSO-d6 , δ): 0.90 (3H, t, J = 7 Hz) ), 1.18 (6H, d, J
= 7Hz), 1.46 (2H, sextet, J = 7Hz), 3.00-3.05 (2H, m),
3.55 (1H, septet, J = 7Hz), 5.68 (2H, s), 6.33 (1H, d, J = 8
Hz), 7.30 (1H, s), 7.72 (1H, dd, J = 2,8Hz), 7.92 (1H,
s), 7.95-7.99 (2H, m), 8.03 (1H, d, J = 8Hz)
【０３４１】製造例128 製造例56と同様にして、下記(1)〜(41)に記載の化合物
を製造した。 (1) ９−（２−クロロベンジル）−５−オキソ−５,６,
７,８−テトラヒドロカルバゾール−２−カルボキサミ
ド mp : 295℃（分解) NMR (DMSO-d6,δ) : 2.13 (2H,m), 2.48 (2H,t,J=7Hz),
2.92 (2H,t,J=7Hz),5.62 (2H,s), 6.41 (1H,d,J=8Hz),
7.21 (1H,t,J=8Hz), 7.27 (1H,br s),7.33 (1H,t,J=8H
z), 7.57 (1H,d,J=8Hz), 7.79 (1H,d,J=8Hz), 7.92(1H,
br s), 8.02 (1H,s), 8.08 (1H,d,J=8Hz) (2) ４−（２−クロロベンジル）−１−オキソ−１,２,
３,４−テトラヒドロシクロペンタ［ｂ］インドール−
６−カルボキサミド mp : >300℃ NMR (DMSO-d6,δ) : 2.88 (2H,m), 2.97 (2H,m), 5.61
(2H,s), 6.81 (1H,d,J=8Hz), 7.27 (1H,t,J=8Hz), 7.36
(1H,br s), 7.38 (1H,t,J=8Hz),7.57 (1H,d,J=8Hz),
7.76 (1H,d,J=8Hz), 7.79 (1H,d,J=8Hz), 7.96(1H,br
s), 8.05 (1H,s)Production Example 128 The following compounds (1) to (41) were produced in the same manner as in Production Example 56. (1) 9- (2-chlorobenzyl) -5-oxo-5,6,
7,8-tetrahydrocarbazole-2-carboxamide mp: 295 ° C. (decomposition) NMR (DMSO-d6 , δ): 2.13 (2H, m), 2.48 (2H, t, J = 7Hz),
2.92 (2H, t, J = 7Hz), 5.62 (2H, s), 6.41 (1H, d, J = 8Hz),
7.21 (1H, t, J = 8Hz), 7.27 (1H, br s), 7.33 (1H, t, J = 8H
z), 7.57 (1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz), 7.92 (1H,
br s), 8.02 (1H, s), 8.08 (1H, d, J = 8Hz) (2) 4- (2-chlorobenzyl) -1-oxo-1,2,
3,4-tetrahydrocyclopenta [b] indole-
6-carboxamide mp:> 300 ° C NMR (DMSO-d6 , δ): 2.88 (2H, m), 2.97 (2H, m), 5.61
(2H, s), 6.81 (1H, d, J = 8Hz), 7.27 (1H, t, J = 8Hz), 7.36
(1H, brs), 7.38 (1H, t, J = 8Hz), 7.57 (1H, d, J = 8Hz),
7.76 (1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz), 7.96 (1H, br
s), 8.05 (1H, s)
【０３４２】(3) １−（２−クロロベンジル）−３−イ
ソブチリル−２−プロピルインドール−７−カルボキサ
ミド mp : 181−183℃ NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.27 (6H,d,J=7
Hz), 1.61 (2H,m),3.02 (2H,m), 3.53 (1H,m), 5.34 (1
H,br s), 5.46 (1H,br s), 5.69(2H,s), 5.99 (1H,d,J=
8Hz), 6.96 (1H,t,J=8Hz), 7.14 (1H,t,J=8Hz),7.15-7.
25 (2H,m), 7.37 (1H,d,J=8Hz), 8.07 (1H,m) (4) １−（２−クロロベンジル）−３−イソブチリル−
２−プロピルインドール−５−カルボキサミド NMR (CDCl3,δ) : 1.03 (3H,t,J=8Hz), 1.32 (6H,d,J=8
Hz), 1.64 (2H,sextet,J=8Hz), 3.06 (2H,t,J=8Hz), 3.
62 (1H,septet,J=8Hz), 5.46(2H,s), 6.26 (1H,d,J=8H
z), 7.05 (1H,t,J=8Hz), 7.20 (1H,t,J=8Hz),7.2 (1H,
d,J=8Hz), 7.47 (1H,d,J=8Hz), 7.65 (1H,d,J=8Hz), 8.
55(1H,s)(3) 1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole-7-carboxamide mp: 181-183 ° C. NMR (CDCl3 , δ): 1.03 (3H, t, J = 7 Hz) ), 1.27 (6H, d, J = 7
Hz), 1.61 (2H, m), 3.02 (2H, m), 3.53 (1H, m), 5.34 (1
H, br s), 5.46 (1H, br s), 5.69 (2H, s), 5.99 (1H, d, J =
8Hz), 6.96 (1H, t, J = 8Hz), 7.14 (1H, t, J = 8Hz), 7.15-7.
25 (2H, m), 7.37 (1H, d, J = 8Hz), 8.07 (1H, m) (4) 1- (2-chlorobenzyl) -3-isobutyryl-
2-propyl-indole-5-carboxamideNMR (CDCl 3, δ): 1.03 (3H, t, J = 8Hz), 1.32 (6H, d, J = 8
Hz), 1.64 (2H, sextet, J = 8Hz), 3.06 (2H, t, J = 8Hz), 3.
62 (1H, septet, J = 8Hz), 5.46 (2H, s), 6.26 (1H, d, J = 8H
z), 7.05 (1H, t, J = 8Hz), 7.20 (1H, t, J = 8Hz), 7.2 (1H,
d, J = 8Hz), 7.47 (1H, d, J = 8Hz), 7.65 (1H, d, J = 8Hz), 8.
55 (1H, s)
【０３４３】(5) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−イソブチリル−２−プロピル
インドール−５−カルボキサミド NMR (CDCl3,δ) : 1.05 (3H,t,J=7Hz), 1.32 (6H,d,J=7
Hz), 1.60-1.72(2H,m), 3.04-3.10 (2H,m), 3.59 (1H,s
eptet,J=7Hz), 5.38 (2H,s),5.74 (1H,s), 5.92 (2H,
s), 6.92 (1H,s), 7.22 (1H,d,J=8Hz), 7.66(1H,dd,J=
1, 8Hz), 8.50 (1H,d,J=1Hz) (6) １−（２−クロロベンジル）−２−プロピルインド
ール−４−カルボキサミド mp : 198−200℃ NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.76 (2H,m),
2.66 (2H,t,J=7Hz),5.41 (2H,s), 6.18 (1H,d,J=8Hz),
6.85 (1H,s), 7.1-7.3 (3H,m), 7.43(1H,d,J=8Hz), 7.5
2 (1H,d,J=8Hz)(5) 1- (6-Chloro-3,4-methylenedioxybenzyl) -3-isobutyryl-2-propylindole-5-carboxamide NMR (CDCl3 , δ): 1.05 (3H, t, J = 7Hz), 1.32 (6H, d, J = 7
Hz), 1.60-1.72 (2H, m), 3.04-3.10 (2H, m), 3.59 (1H, s
eptet, J = 7Hz), 5.38 (2H, s), 5.74 (1H, s), 5.92 (2H,
s), 6.92 (1H, s), 7.22 (1H, d, J = 8Hz), 7.66 (1H, dd, J =
1,8Hz), 8.50 (1H, d, J = 1Hz) (6) 1- (2-chlorobenzyl) -2-propylindole-4-carboxamide mp: 198-200 ° C NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.76 (2H, m),
2.66 (2H, t, J = 7Hz), 5.41 (2H, s), 6.18 (1H, d, J = 8Hz),
6.85 (1H, s), 7.1-7.3 (3H, m), 7.43 (1H, d, J = 8Hz), 7.5
2 (1H, d, J = 8Hz)
【０３４４】(7) ９−（２−クロロベンジル）−８−オ
キソ−５,６,７,８−テトラヒドロカルバゾール−２−
カルボキサミド mp : 255℃（分解） NMR (DMSO-d6,δ) : 2.18 (2H,m), 2.56 (2H,t,J=7Hz),
3.07 (2H,t,J=7Hz),5.88 (2H,s), 6.08 (1H,d,J=8Hz),
7.11 (1H,t,J=8Hz), 7.25 (1H,t,J=8Hz), 7.36 (1H,br
s), 7.52 (1H,d,J=8Hz), 7.72 (1H,d,J=8Hz),7.85 (1
H,d,J=8Hz), 8.02 (2H,m) (8) ９−（６−クロロ−３,４−メチレンジオキシベン
ジル）−８−オキソ−５,６,７,８−テトラヒドロカル
バゾール−２−カルボキサミド mp : 270℃（分解） NMR (DMSO-d6,δ) : 2.17 (2H,m), 2.58 (2H,t,J=7Hz),
3.08 (2H,t,J=7Hz),5.52 (1H,s), 5.78 (2H,s), 5.96
(2H,s), 7.17 (1H,s), 7.40 (1H,br s), 7.71 (1H,d,J=
8Hz), 7.86 (1H,d,J=8Hz), 7.96 (1H,s), 8.01(1H,br
s)(7) 9- (2-chlorobenzyl) -8-oxo-5,6,7,8-tetrahydrocarbazole-2-
Carboxamide mp: 255 ° C (decomposition) NMR (DMSO-d6 , δ): 2.18 (2H, m), 2.56 (2H, t, J = 7Hz),
3.07 (2H, t, J = 7Hz), 5.88 (2H, s), 6.08 (1H, d, J = 8Hz),
7.11 (1H, t, J = 8Hz), 7.25 (1H, t, J = 8Hz), 7.36 (1H, br
s), 7.52 (1H, d, J = 8Hz), 7.72 (1H, d, J = 8Hz), 7.85 (1
(H, d, J = 8Hz), 8.02 (2H, m) (8) 9- (6-chloro-3,4-methylenedioxybenzyl) -8-oxo-5,6,7,8-tetrahydrocarbazole- 2-carboxamide mp: 270 ° C (decomposition) NMR (DMSO-d6 , δ): 2.17 (2H, m), 2.58 (2H, t, J = 7Hz),
3.08 (2H, t, J = 7Hz), 5.52 (1H, s), 5.78 (2H, s), 5.96
(2H, s), 7.17 (1H, s), 7.40 (1H, br s), 7.71 (1H, d, J =
8Hz), 7.86 (1H, d, J = 8Hz), 7.96 (1H, s), 8.01 (1H, br
s)
【０３４５】(9) １−（４−ブロモ−２−クロロベンジ
ル）−３−イソブチリル−２−プロピルインドール−６
−カルボキサミド mp : 199−201℃ IR (KBr) : 3382, 1654, 1619, 1488, 1404 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.54-1.66 (2H,m), 3.00-3.05 (2H,m), 3.50-3.60
(1H,m), 5.45 (2H,s), 6.09 (1H,t,J=7.5Hz), 7.17 (1
H,dd,J=7.5, 2Hz), 7.62 (1H,dd,J=7.5, 2Hz), 7.65(1
H,d,J=2Hz), 7.83 (1H,s), 7.99 (1H,d,J=7.5Hz) MASS (m/z) : 477 (M++2) (10) １−（２−クロロベンジル）−３−モルホリノア
セチル−２−プロピルインドール−６−カルボキサミド IR (KBr) : 1654, 1616, 1452 cm-1 NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.58-1.68 (2H,
m), 2.73 (4H,t,J=6.5Hz), 3.05-3.10 (2H,m), 3.84 (4
H,t,J=6.5Hz), 3.89 (2H,s), 5.51(2H,s), 6.23 (1H,d,
J=7.5Hz), 7.05 (1H,t,J=7.5Hz), 7.22 (1H,t,J=7.5H
z), 7.46 (1H,d,J=7.5Hz), 7.64 (1H,d,J=7.5Hz), 7.84
(1H,s),7.98 (1H,d,J=7.5Hz) MASS (m/z) : 454 (M++1)(9) 1- (4-bromo-2-chlorobenzyl) -3-isobutyryl-2-propylindole-6
-Carboxamide mp: 199-201 ° C IR (KBr): 3382, 1654, 1619, 1488, 1404 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.54-1.66 (2H, m), 3.00-3.05 (2H, m), 3.50-3.60
(1H, m), 5.45 (2H, s), 6.09 (1H, t, J = 7.5Hz), 7.17 (1
H, dd, J = 7.5,2Hz), 7.62 (1H, dd, J = 7.5,2Hz), 7.65 (1
H, d, J = 2Hz), 7.83 (1H, s), 7.99 (1H, d, J = 7.5Hz) MASS (m / z): 477 (M++ 2) (10) 1- (2-chloro (Benzyl) -3-morpholinoacetyl-2-propylindole-6-carboxamide IR (KBr): 1654, 1616, 1452 cm-1 NMR (CDCl3 , δ): 1.02 (3H, t, J = 7 Hz), 1.58- 1.68 (2H,
m), 2.73 (4H, t, J = 6.5Hz), 3.05-3.10 (2H, m), 3.84 (4
H, t, J = 6.5Hz), 3.89 (2H, s), 5.51 (2H, s), 6.23 (1H, d,
J = 7.5Hz), 7.05 (1H, t, J = 7.5Hz), 7.22 (1H, t, J = 7.5H
z), 7.46 (1H, d, J = 7.5Hz), 7.64 (1H, d, J = 7.5Hz), 7.84
(1H, s), 7.98 (1H, d, J = 7.5Hz) MASS (m / z): 454 (M+ +1)
【０３４６】(11) １−（２−クロロベンジル）−３−
（Ｎ,Ｎ−ジメチルカルバモイル）−２−プロピルイン
ドール−６−カルボン酸メチルエステル IR (KBr) : 1703, 1610 cm-1 NMR (CDCl3,δ) : 0.94 (3H,t,J=7Hz), 1.56-1.63 (2H,
m), 2.76-2.87 (2H,m), 3.11 (6H,br s), 3.90 (3H,s),
5.49 (2H,s), 6.29 (1H,d,J=7.5Hz),7.04 (1H,t,J=7.5
Hz), 7.21 (1H,t,J=7.5Hz), 7.45 (1H,d,J=7.5Hz),7.49
(1H,d,J=7.5Hz), 7.86 (1H,d,J=7.5Hz), 7.90 (1H,s) MASS (m/z) : 413 (M++1) (12) １−（２−クロロベンジル）−３−（モルホリノ
カルボニル）−２−プロピルインドール−６−カルボン
酸メチルエステル IR (KBr) : 1715, 1617, 1277, 1227 cm-1 NMR (CDCl3,δ) : 0.85 (3H,t,J=7Hz), 1.56-1.63 (2H,
m), 2.82-2.90 (2H,m), 3.69 (6H,br s), 3.77 (2H,br
s), 3.90 (3H,s), 5.48 (2H,s), 6.29(1H,d,J=7.5Hz),
7.04 (1H,t,J=7.5Hz), 7.21 (1H,ddd,J=7.5, 7.5,2Hz),
7.45 (1H,d,J=7.5Hz), 7.54 (1H,d,J=7.5Hz), 7.88 (1
H,s), 7.91(1H,d,J=2Hz) MASS (m/z) : 455 (M++1), 76 (bp)(11) 1- (2-chlorobenzyl) -3-
(N, N-dimethylcarbamoyl) -2-propylindole-6-carboxylic acid methyl ester IR (KBr): 1703, 1610 cm-1 NMR (CDCl3 , δ): 0.94 (3H, t, J = 7 Hz), 1.56-1.63 (2H,
m), 2.76-2.87 (2H, m), 3.11 (6H, br s), 3.90 (3H, s),
5.49 (2H, s), 6.29 (1H, d, J = 7.5Hz), 7.04 (1H, t, J = 7.5
Hz), 7.21 (1H, t, J = 7.5Hz), 7.45 (1H, d, J = 7.5Hz), 7.49
(1H, d, J = 7.5Hz), 7.86 (1H, d, J = 7.5Hz), 7.90 (1H, s) MASS (m / z): 413 (M++ 1) (12) 1- (2 -Chlorobenzyl) -3- (morpholinocarbonyl) -2-propylindole-6-carboxylic acid methyl ester IR (KBr): 1715, 1617, 1277, 1227 cm-1 NMR (CDCl3 , δ): 0.85 (3H, t, J = 7Hz), 1.56-1.63 (2H,
m), 2.82-2.90 (2H, m), 3.69 (6H, br s), 3.77 (2H, br
s), 3.90 (3H, s), 5.48 (2H, s), 6.29 (1H, d, J = 7.5Hz),
7.04 (1H, t, J = 7.5Hz), 7.21 (1H, ddd, J = 7.5,7.5,2Hz),
7.45 (1H, d, J = 7.5Hz), 7.54 (1H, d, J = 7.5Hz), 7.88 (1
H, s), 7.91 (1H, d, J = 2Hz) MASS (m / z): 455 (M+ +1), 76 (bp)
【０３４７】(13) ６−カルバモイル−１−（２−クロ
ロベンジル）−Ｎ,Ｎ−ジメチル−２−プロピルインド
ール−３−カルボキサミド mp : 213−214℃ IR (KBr) : 1676, 1601 cm-1 NMR (CDCl3,δ) : 0.93 (3H,t,J=7Hz), 1.52-1.62 (2H,
m), 2.76-2.86 (2H,m), 3.12 (6H,br s), 5.47 (2H,s),
6.27 (1H,d,J=7.5Hz), 7.03 (1H,t,J=7.5Hz), 7.20 (1
H,t,J=7.5Hz), 7.44 (1H,d,J=7.5Hz), 7.49-7.54 (2H,
m), 7.78 (1H,s) MASS (m/z) : 398 (M++1), 76 (bp) (14) １−（２−クロロベンジル）−３−（モルホリノ
カルボニル）−２−プロピルインドール−６−カルボキ
サミド mp : 229−230℃ IR (KBr) : 3448, 3359, 3326, 1675, 1606 cm-1 NMR (CDCl3,δ) : 0.95 (3H,t,J=7Hz), 1.57-1.62 (2H,
m), 2.82-2.89 (2H,m), 3.69 (6H,br s), 3.78 (2H,br
s), 5.49 (2H,s), 6.28 (1H,d,J=7.5Hz), 7.04 (1H,t,J
=7.5Hz), 7.21 (1H,t,J=7.5Hz), 7.45 (1H,t,J=7.5Hz),
7.55 (2H,s), 7.80 (1H,s) MASS (m/z) : 440 (M++1), 76 (bp)(13) 6-carbamoyl-1- (2-chlorobenzyl) -N, N-dimethyl-2-propylindole-3-carboxamide mp: 213-214 ° C IR (KBr): 1676, 1601 cm-1 NMR (CDCl3 , δ): 0.93 (3H, t, J = 7Hz), 1.52-1.62 (2H,
m), 2.76-2.86 (2H, m), 3.12 (6H, br s), 5.47 (2H, s),
6.27 (1H, d, J = 7.5Hz), 7.03 (1H, t, J = 7.5Hz), 7.20 (1
H, t, J = 7.5Hz), 7.44 (1H, d, J = 7.5Hz), 7.49-7.54 (2H,
m), 7.78 (1H, s) MASS (m / z): 398 (M+ +1), 76 (bp) (14) 1- (2-chlorobenzyl) -3- (morpholinocarbonyl) -2-propyl Indole-6-carboxamide mp: 229-230 ° C IR (KBr): 3448, 3359, 3326, 1675, 1606 cm-1 NMR (CDCl3 , δ): 0.95 (3H, t, J = 7Hz), 1.57-1.62 (2H,
m), 2.82-2.89 (2H, m), 3.69 (6H, br s), 3.78 (2H, br
s), 5.49 (2H, s), 6.28 (1H, d, J = 7.5Hz), 7.04 (1H, t, J
= 7.5Hz), 7.21 (1H, t, J = 7.5Hz), 7.45 (1H, t, J = 7.5Hz),
7.55 (2H, s), 7.80 (1H, s) MASS (m / z): 440 (M+ +1), 76 (bp)
【０３４８】(15) １−（２−クロロベンジル）−２−
プロピルインドール−３,６−ジカルボキサミド mp : 296℃（分解） IR (KBr) : 3376, 3188, 1644, 1613 cm-1 NMR (DMSO-d6,δ) : 0.88 (3H,t,J=7Hz), 1.40-1.51 (2
H,m), 2.98 (2H,t,J=7Hz), 5.57 (2H,s), 6.17 (1H,d,J
=7.5Hz), 7.14-7.35 (6H,m), 7.58(1H,d,J=7.5Hz), 7.7
3 (1H,d,J=7.5Hz), 7.83-7.89 (1H,m), 7.95 (1H,s) MASS (m/z) : 370 (M++1), 86 (bp) (16) １−（２−クロロベンジル）−２−エチル−３−
ホルミルインドール−６−カルボキサミド mp : 260−261℃ IR (KBr) : 3400, 1685, 1635, 1615, 1390 cm-1 NMR (CDCl3,δ) : 1.29 (3H,t,J=7Hz), 3.08 (2H,q,J=7
Hz), 5.52 (2H,s),6.29 (1H,d,J=7.5Hz), 7.07 (1H,t,J
=7.5Hz), 7.24 (1H,t,J=7.5Hz),7.49 (1H,d,J=7.5Hz),
7.69 (1H,d,J=7.5Hz), 7.86 (1H,s), 8.35 (1H,d,J=7.5
Hz), 10.24 (1H,s) MASS (m/z) : 341 (M++1)(15) 1- (2-chlorobenzyl) -2-
Propylindole-3,6-dicarboxamide mp: 296 ° C. (decomposition) IR (KBr): 3376, 3188, 1644, 1613 cm−1 NMR (DMSO-d6 , δ): 0.88 (3H, t, J = 7 Hz) ), 1.40-1.51 (2
H, m), 2.98 (2H, t, J = 7Hz), 5.57 (2H, s), 6.17 (1H, d, J
= 7.5Hz), 7.14-7.35 (6H, m), 7.58 (1H, d, J = 7.5Hz), 7.7
3 (1H, d, J = 7.5Hz), 7.83-7.89 (1H, m), 7.95 (1H, s) MASS (m / z): 370 (M+ +1), 86 (bp) (16) 1 -(2-chlorobenzyl) -2-ethyl-3-
Formylindole-6-carboxamide mp: 260-261 ° C IR (KBr): 3400, 1685, 1635, 1615, 1390 cm-1 NMR (CDCl3 , δ): 1.29 (3H, t, J = 7Hz), 3.08 ( 2H, q, J = 7
Hz), 5.52 (2H, s), 6.29 (1H, d, J = 7.5Hz), 7.07 (1H, t, J
= 7.5Hz), 7.24 (1H, t, J = 7.5Hz), 7.49 (1H, d, J = 7.5Hz),
7.69 (1H, d, J = 7.5Hz), 7.86 (1H, s), 8.35 (1H, d, J = 7.5
Hz), 10.24 (1H, s) MASS (m / z): 341 (M+ +1)
【０３４９】(17) １−（２−クロロベンゾイル）−３
−イソブチリル−２−プロピルインドール−６−カルボ
キサミド mp : 125−126.5℃ IR (KBr) : 1700, 1650 cm-1 NMR (CDCl3,δ) : 0.90 (3H,t,J=7Hz), 1.28 (6H,d,J=7
Hz), 1.61-1.74(2H,m), 2.98-3.05 (2H,m), 3.40-3.49
(1H,m), 7.48-7.53 (3H,m),7.59-7.65 (2H,m), 7.79 (2
H,AB,J=8, 7.5Hz) MASS (m/z) : 411 (M++1), 76 (bp) (18) １−（２−クロロベンジル）−３−ホルミルイン
ドール−６−カルボキサミド mp : 237−240℃ NMR (DMSO-d6,δ) : 5.68 (2H,s), 6.86 (1H,d,J=8Hz),
6.25-6.4 (3H,m),7.58 (1H,d,J=8Hz), 7.84 (1H,d,J=8
Hz), 7.98 (1H,br s), 8.14 (1H,s), 8.17 (1H,d,J=8H
z), 8.46 (1H,s), 9.98 (1H,s)(17) 1- (2-chlorobenzoyl) -3
-Isobutyryl-2-propylindole-6-carboxamide mp: 125-126.5 ° C IR (KBr): 1700, 1650 cm-1 NMR (CDCl3 , δ): 0.90 (3H, t, J = 7Hz), 1.28 (6H , d, J = 7
Hz), 1.61-1.74 (2H, m), 2.98-3.05 (2H, m), 3.40-3.49
(1H, m), 7.48-7.53 (3H, m), 7.59-7.65 (2H, m), 7.79 (2
H, AB, J = 8, 7.5 Hz) MASS (m / z): 411 (M+ +1), 76 (bp) (18) 1- (2-chlorobenzyl) -3-formylindole-6-carboxamide mp: 237-240 ° C NMR (DMSO-d6 , δ): 5.68 (2H, s), 6.86 (1H, d, J = 8Hz),
6.25-6.4 (3H, m), 7.58 (1H, d, J = 8Hz), 7.84 (1H, d, J = 8
Hz), 7.98 (1H, br s), 8.14 (1H, s), 8.17 (1H, d, J = 8H
z), 8.46 (1H, s), 9.98 (1H, s)
【０３５０】(19) ３−アセチル−１−（２−クロロベ
ンジル）−２−メチルインドール−６−カルボキサミド mp : 272−276℃ NMR (DMSO-d6,δ) : 2.63 (3H,s), 2.65 (3H,s), 5.61
(2H,s), 6.17 (1H,d,J=8Hz), 7.18 (1H,t,J=8Hz), 7.27
(1H,br s), 7.32 (1H,t,J=8Hz),7.57 (1H,d,J=8Hz),
7.80 (1H,d,J=8Hz), 7.94 (1H,br s), 8.03 (1H,s),8.1
1 (1H,s) (20) １−（２−クロロベンジル）−２−メチル−３−
プロピオニルインドール−６−カルボキサミド mp : 215−217℃ NMR (DMSO-d6,δ) : 1.14 (3H,t,J=7Hz), 2.64 (3H,s),
3.04 (2H,q,J=7Hz),5.62 (2H,s), 6.18 (1H,d,J=8Hz),
7.18 (1H,t,J=8Hz), 7.29 (1H,br s),7.32 (1H,t,J=8H
z), 7.57 (1H,d,J=8Hz), 7.79 (1H,d,J=8Hz), 8.02 (1
H,s), 8.10 (1H,d,J=8Hz)(19) 3-acetyl-1- (2-chlorobenzyl) -2-methylindole-6-carboxamide mp: 272-276 ° C. NMR (DMSO-d6 , δ): 2.63 (3H, s), 2.65 (3H, s), 5.61
(2H, s), 6.17 (1H, d, J = 8Hz), 7.18 (1H, t, J = 8Hz), 7.27
(1H, brs), 7.32 (1H, t, J = 8Hz), 7.57 (1H, d, J = 8Hz),
7.80 (1H, d, J = 8Hz), 7.94 (1H, br s), 8.03 (1H, s), 8.1
1 (1H, s) (20) 1- (2-chlorobenzyl) -2-methyl-3-
Propionylindole-6-carboxamide mp: 215-217 ° C NMR (DMSO-d6 , δ): 1.14 (3H, t, J = 7Hz), 2.64 (3H, s),
3.04 (2H, q, J = 7Hz), 5.62 (2H, s), 6.18 (1H, d, J = 8Hz),
7.18 (1H, t, J = 8Hz), 7.29 (1H, br s), 7.32 (1H, t, J = 8H
z), 7.57 (1H, d, J = 8Hz), 7.79 (1H, d, J = 8Hz), 8.02 (1
H, s), 8.10 (1H, d, J = 8Hz)
【０３５１】(21) １−（２−クロロベンゾ［ｂ］チオ
フェン−３−イルメチル）−３−イソブチリル−２−メ
チルインドール−６−カルボキサミド mp : 255℃（分解） NMR (DMSO-d6,δ) : 1.13 (6H,d,J=7Hz), 2.63 (3H,s),
3.47 (1H,m), 5.84(2H,s), 7.2-7.42 (4H,m), 7.48 (1
H,d,J=8Hz), 7.89 (1H,br s), 7.95-8.0 (2H,m), 8.23
(1H,s) (22) １−（ベンゾチアゾール−２−イルメチル）−２
−エチル−３−イソブチリルインドール−６−カルボキ
サミド mp : 188−190.5℃（分解） NMR (CDCl3,δ) : 1.28 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 3.27 (2H,q,J=7Hz), 3.53 (1H,m), 5.82 (2H,s),
7.36 (1H,t,J=8Hz), 7.49 (1H,t,J=8Hz), 7.66 (1H,d,J
=8Hz), 7.74 (1H,d,J=8Hz), 7.97 (1H,d,J=8Hz),8.02
(1H,d,J=8Hz), 8.07 (1H,s)(21) 1- (2-chlorobenzo [b] thiophen-3-ylmethyl) -3-isobutyryl-2-methylindole-6-carboxamide mp: 255 ° C. (decomposition) NMR (DMSO-d6 , δ) : 1.13 (6H, d, J = 7Hz), 2.63 (3H, s),
3.47 (1H, m), 5.84 (2H, s), 7.2-7.42 (4H, m), 7.48 (1
(H, d, J = 8Hz), 7.89 (1H, brs), 7.95-8.0 (2H, m), 8.23
(1H, s) (22) 1- (benzothiazol-2-ylmethyl) -2
-Ethyl-3-isobutyrylindole-6-carboxamide mp: 188-190.5 ° C (decomposition) NMR (CDCl3 , δ): 1.28 (3H, t, J = 7Hz), 1.29 (6H, d, J = 7
Hz), 3.27 (2H, q, J = 7Hz), 3.53 (1H, m), 5.82 (2H, s),
7.36 (1H, t, J = 8Hz), 7.49 (1H, t, J = 8Hz), 7.66 (1H, d, J
= 8Hz), 7.74 (1H, d, J = 8Hz), 7.97 (1H, d, J = 8Hz), 8.02
(1H, d, J = 8Hz), 8.07 (1H, s)
【０３５２】(23) １−（ベンゾ［ｂ］チオフェン−５
−イルメチル）−３−イソブチリル−２−プロピルイン
ドール−６−カルボキサミド mp : 189−192℃（分解） NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 1.62 (2H,m),3.14 (2H,m), 3.57 (1H,m), 5.58 (2
H,s), 7.02 (1H,d,J=8Hz), 7.18(1H,d,J=6Hz), 7.29 (1
H,s), 7.43 (1H,d,J=6Hz), 7.60 (1H,d,J=8Hz),7.79 (1
H,d,J=8Hz), 7.92 (1H,s), 7.97 (1H,d,J=8Hz) (24) １−（２,４−ジクロロベンジル）−３−イソブチ
リル−２−プロピルインドール−６−カルボキサミド mp : 191−192℃ NMR (DMSO-d6,δ) : 0.92 (3H,t,J=7Hz), 1.18 (6H,d,J
=7Hz), 1.45 (2H,sextet,J=7Hz), 3.00-3.05 (2H,m),
3.55 (2H,septet,J=7Hz), 5.60 (2H,s), 6.18 (1H,d,J=
8Hz), 7.28 (1H,dd,J=2, 8Hz), 7.31 (1H,s), 7.76(1H,
d,J=2Hz), 7.82 (1H,d,J=8Hz), 7.92 (1H,br s), 7.94
(1H,s), 7.98(1H,d,J=8Hz)(23) 1- (benzo [b] thiophene-5
-Ylmethyl) -3-isobutyryl-2-propylindole-6-carboxamide mp: 189-192 ° C (decomposition) NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.31 (6H, d, J = 7
Hz), 1.62 (2H, m), 3.14 (2H, m), 3.57 (1H, m), 5.58 (2
H, s), 7.02 (1H, d, J = 8Hz), 7.18 (1H, d, J = 6Hz), 7.29 (1
H, s), 7.43 (1H, d, J = 6Hz), 7.60 (1H, d, J = 8Hz), 7.79 (1
(H, d, J = 8Hz), 7.92 (1H, s), 7.97 (1H, d, J = 8Hz) (24) 1- (2,4-dichlorobenzyl) -3-isobutyryl-2-propylindole-6 -Carboxamide mp: 191-192 ° C NMR (DMSO-d6 , δ): 0.92 (3H, t, J = 7Hz), 1.18 (6H, d, J
= 7Hz), 1.45 (2H, sextet, J = 7Hz), 3.00-3.05 (2H, m),
3.55 (2H, septet, J = 7Hz), 5.60 (2H, s), 6.18 (1H, d, J =
8Hz), 7.28 (1H, dd, J = 2,8Hz), 7.31 (1H, s), 7.76 (1H,
d, J = 2Hz), 7.82 (1H, d, J = 8Hz), 7.92 (1H, br s), 7.94
(1H, s), 7.98 (1H, d, J = 8Hz)
【０３５３】(25) ３−イソブチリル−２−プロピル−
１−（３−ピリジルメチル）インドール−６−カルボキ
サミド mp : 230−235℃ NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.60 (2H,sextet,J=7Hz), 3.08-3.16 (2H,m), 3.5
6 (2H,septet,J=7Hz), 5.48(2H,s), 7.19-7.24 (2H,m),
7.61 (1H,d,J=8Hz), 7.92 (1H,s), 7.96(1H,d,J=8Hz),
8.38 (1H,d,J=2Hz), 8.52 (1H,dd,J=2, 5Hz) (26) ３−イソブチリル−２−プロピル−１−（１−ナ
フチルメチル）インドール−６−カルボキサミド mp : 202−203℃ NMR (CDCl3,δ) : 0.96 (3H,t,J=7Hz), 1.34 (6H,d,J=7
Hz), 1.61-1.68 (2H,m), 3.08 (2H,dd,J=7, 8Hz), 3.61
(1H,septet,J=7Hz), 5.90 (2H,s),6.28 (1H,d,J=8Hz),
7.21 (1H,t,J=8Hz), 7.58-7.69 (3H,m), 7.76 (1H,d,J
=8Hz), 7.78 (1H,s), 7.94 (1H,d,J=8Hz), 8.00 (1H,d,
J=8Hz), 8.08(1H,d,J=8Hz)(25) 3-isobutyryl-2-propyl-
1- (3-pyridylmethyl) indole-6-carboxamide mp: 230-235 ° C NMR (CDCl3 , δ): 1.02 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7)
Hz), 1.60 (2H, sextet, J = 7Hz), 3.08-3.16 (2H, m), 3.5
6 (2H, septet, J = 7Hz), 5.48 (2H, s), 7.19-7.24 (2H, m),
7.61 (1H, d, J = 8Hz), 7.92 (1H, s), 7.96 (1H, d, J = 8Hz),
8.38 (1H, d, J = 2Hz), 8.52 (1H, dd, J = 2,5Hz) (26) 3-isobutyryl-2-propyl-1- (1-naphthylmethyl) indole-6-carboxamide mp: 202 -203 ° C NMR (CDCl3 , δ): 0.96 (3H, t, J = 7Hz), 1.34 (6H, d, J = 7
Hz), 1.61-1.68 (2H, m), 3.08 (2H, dd, J = 7,8Hz), 3.61
(1H, septet, J = 7Hz), 5.90 (2H, s), 6.28 (1H, d, J = 8Hz),
7.21 (1H, t, J = 8Hz), 7.58-7.69 (3H, m), 7.76 (1H, d, J
= 8Hz), 7.78 (1H, s), 7.94 (1H, d, J = 8Hz), 8.00 (1H, d,
J = 8Hz), 8.08 (1H, d, J = 8Hz)
【０３５４】(27) ３−イソブチリル−２−プロピル−
１−（２−ナフチルメチル）インドール−６−カルボキ
サミド mp : 189−190℃ NMR (CDCl3,δ) : 0.98 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.55-1.68 (2H,m), 3.14-3.18 (2H,m), 3.58 (1H,
septet,J=7Hz), 5.58 (2H,s), 7.15(1H,dd,J=1, 8Hz),
7.28 (1H,s), 7.42-7.48 (2H,m), 7.60-7.66 (2H,m),7.
78 (2H,d,J=8Hz), 7.93 (1H,d,J=1Hz), 7.98 (1H,d,J=8
Hz) (28) １−アリル−３−イソブチリル−２−プロピルイ
ンドール−６−カルボキサミド mp : 155−158℃ NMR (CDCl3,δ) : 1.06 (3H,t,J=7Hz), 1.27 (6H,d,J=7
Hz), 1.71 (2H,m),3.11 (2H,m), 3.51 (1H,m), 4.83 (2
H,m), 4.86 (1H,m), 5.19 (1H,m),5.96 (1H,m), 7.58
(1H,d,J=8Hz), 7.89 (1H,d,J=8Hz), 7.96 (1H,s)(27) 3-isobutyryl-2-propyl-
1- (2-naphthylmethyl) indole-6-carboxamide mp: 189-190 ° C. NMR (CDCl3 , δ): 0.98 (3H, t, J = 7 Hz), 1.30 (6H, d, J = 7)
Hz), 1.55-1.68 (2H, m), 3.14-3.18 (2H, m), 3.58 (1H,
septet, J = 7Hz), 5.58 (2H, s), 7.15 (1H, dd, J = 1,8Hz),
7.28 (1H, s), 7.42-7.48 (2H, m), 7.60-7.66 (2H, m), 7.
78 (2H, d, J = 8Hz), 7.93 (1H, d, J = 1Hz), 7.98 (1H, d, J = 8
Hz) (28) 1-allyl-3-isobutyryl-2-propylindole-6-carboxamide mp: 155-158 ° C NMR (CDCl3 , δ): 1.06 (3H, t, J = 7Hz), 1.27 (6H, d, J = 7
Hz), 1.71 (2H, m), 3.11 (2H, m), 3.51 (1H, m), 4.83 (2
H, m), 4.86 (1H, m), 5.19 (1H, m), 5.96 (1H, m), 7.58
(1H, d, J = 8Hz), 7.89 (1H, d, J = 8Hz), 7.96 (1H, s)
【０３５５】(29) １−（２−クロロベンジル）−３−
イソブチリル−２−（１−プロペニル）インドール−６
−カルボキサミド mp : 190−193℃ NMR (CDCl3,δ) : 1.23 (6H,d,J=7Hz), 1.93 (3H,d,J=7
Hz), 3.51 (1H,m),5.48 (2H,s), 5.91 (1H,dq,J=15, 7H
z), 6.41 (1H,d,J=8Hz), 6.71 (1H,d,J=15Hz), 7.07 (1
H,t,J=8Hz), 7.23 (1H,t,J=8Hz), 7.46 (1H,d,J=8Hz),
7.62 (1H,d,J=8Hz), 7.80 (1H,s), 8.24 (1H,d,J=8Hz) (30) １−（２−クロロベンジル）−２−（１−ヒドロ
キシプロピル）−３−イソブチリルインドール−６−カ
ルボキサミド mp : 220−223℃ NMR (CDCl3,δ) : 0.94 (3H,t,J=7Hz), 1.32 (3H,d,J=7
Hz), 1.39 (3H,d,J=7Hz), 1.52 (1H,m), 1.93 (1H,m),
3.69 (1H,m), 4.68 (1H,m), 5.48(1H,d,J=17Hz), 5.66
(1H,d,J=17Hz), 6.33 (1H,d,J=10Hz), 6.43 (1H,d,J=8H
z), 7.07 (1H,t,J=8Hz), 7.21 (1H,t,J=8Hz), 7.44 (1
H,d,J=8Hz),7.68 (1H,d,J=8Hz), 7.92 (1H,s), 7.96 (1
H,d,J=8Hz)(29) 1- (2-chlorobenzyl) -3-
Isobutyryl-2- (1-propenyl) indole-6
-Carboxamide mp: 190-193 ° C NMR (CDCl3 , δ): 1.23 (6H, d, J = 7Hz), 1.93 (3H, d, J = 7
Hz), 3.51 (1H, m), 5.48 (2H, s), 5.91 (1H, dq, J = 15, 7H
z), 6.41 (1H, d, J = 8Hz), 6.71 (1H, d, J = 15Hz), 7.07 (1
(H, t, J = 8Hz), 7.23 (1H, t, J = 8Hz), 7.46 (1H, d, J = 8Hz),
7.62 (1H, d, J = 8Hz), 7.80 (1H, s), 8.24 (1H, d, J = 8Hz) (30) 1- (2-chlorobenzyl) -2- (1-hydroxypropyl) -3 -Isobutyrylindole-6-carboxamide mp: 220-223 ° C NMR (CDCl3 , δ): 0.94 (3H, t, J = 7Hz), 1.32 (3H, d, J = 7
Hz), 1.39 (3H, d, J = 7Hz), 1.52 (1H, m), 1.93 (1H, m),
3.69 (1H, m), 4.68 (1H, m), 5.48 (1H, d, J = 17Hz), 5.66
(1H, d, J = 17Hz), 6.33 (1H, d, J = 10Hz), 6.43 (1H, d, J = 8H
z), 7.07 (1H, t, J = 8Hz), 7.21 (1H, t, J = 8Hz), 7.44 (1
H, d, J = 8Hz), 7.68 (1H, d, J = 8Hz), 7.92 (1H, s), 7.96 (1
(H, d, J = 8Hz)
【０３５６】(31) １−（２−クロロベンジル）−３−
（３,３−ジメチルブタノイル）インドール−６−カル
ボキサミド mp : 202−205℃ NMR (CDCl3,δ) : 1.08 (9H,s), 2.69 (2H,s), 5.50 (2
H,s), 6.73 (1H,d,J=8Hz), 7.14 (1H,t,J=8Hz), 7.28
(1H,t,J=8Hz), 7.45 (1H,d,J=8Hz),7.62 (1H,d,J=8Hz),
7.80 (1H,s), 7.99 (1H,s), 8.53 (1H,d,J=8Hz) (32) １−（２−クロロベンジル）−２−プロピルイン
ドール−６−カルボキサミド mp : 174−177℃ NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.74 (2H,m),
2.61 (2H,t,J=7Hz),5.43 (2H,s), 6.15 (1H,d,J=8Hz),
6.44 (1H,s), 7.00 (1H,t,J=8Hz),7.18 (1H,t,J=8Hz),
7.4-7.5 (2H,m), 7.61 (1H,d,J=8Hz), 7.79 (1H,s)(31) 1- (2-chlorobenzyl) -3-
(3,3-dimethylbutanoyl) indole-6-carboxamide mp: 202-205 ° C. NMR (CDCl3 , δ): 1.08 (9H, s), 2.69 (2H, s), 5.50 (2
H, s), 6.73 (1H, d, J = 8Hz), 7.14 (1H, t, J = 8Hz), 7.28
(1H, t, J = 8Hz), 7.45 (1H, d, J = 8Hz), 7.62 (1H, d, J = 8Hz),
7.80 (1H, s), 7.99 (1H, s), 8.53 (1H, d, J = 8Hz) (32) 1- (2-chlorobenzyl) -2-propylindole-6-carboxamide mp: 174-177 ° C NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.74 (2H, m),
2.61 (2H, t, J = 7Hz), 5.43 (2H, s), 6.15 (1H, d, J = 8Hz),
6.44 (1H, s), 7.00 (1H, t, J = 8Hz), 7.18 (1H, t, J = 8Hz),
7.4-7.5 (2H, m), 7.61 (1H, d, J = 8Hz), 7.79 (1H, s)
【０３５７】(33) １−（２−ブロモベンジル）−２−
プロピルインドール−６−カルボキサミド mp : 166−168℃ NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.73 (2H,m),
2.59 (2H,m), 5.36(2H,s), 6.10 (1H,d,J=8Hz), 6.42
(1H,s), 7.0-7.15 (2H,m), 7.46(1H,dd,J=1, 8Hz), 7.6
1 (1H,dd,J=1, 8Hz), 7.76 (1H,s) (34) ２−アセチル−１−（２−クロロベンジル）−３
−メチルインドール−６−カルボキサミド mp : 234−236℃ NMR (DMSO-d6,δ) : 2.58 (3H,s), 2.71 (3H,s), 5.79
(2H,s), 6.03 (1H,d,J=8Hz), 7.09 (1H,t,J=8Hz), 7.24
(1H,t,J=8Hz), 7.35 (1H,br s),7.50 (1H,d,J=8Hz),
7.70 (1H,d,J=8Hz), 7.92 (1H,d,J=8Hz), 7.98 (1H,s),
7.99 (1H,br s)(33) 1- (2-bromobenzyl) -2-
Propylindole-6-carboxamide mp: 166-168 ° C NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.73 (2H, m),
2.59 (2H, m), 5.36 (2H, s), 6.10 (1H, d, J = 8Hz), 6.42
(1H, s), 7.0-7.15 (2H, m), 7.46 (1H, dd, J = 1,8Hz), 7.6
1 (1H, dd, J = 1,8Hz), 7.76 (1H, s) (34) 2-acetyl-1- (2-chlorobenzyl) -3
-Methylindole-6-carboxamide mp: 234-236 ° C NMR (DMSO-d6 , δ): 2.58 (3H, s), 2.71 (3H, s), 5.79
(2H, s), 6.03 (1H, d, J = 8Hz), 7.09 (1H, t, J = 8Hz), 7.24
(1H, t, J = 8Hz), 7.35 (1H, br s), 7.50 (1H, d, J = 8Hz),
7.70 (1H, d, J = 8Hz), 7.92 (1H, d, J = 8Hz), 7.98 (1H, s),
7.99 (1H, br s)
【０３５８】(35) ２−クロロ−１−（２−クロロベン
ジル）−３−エチルインドール−６−カルボキサミド mp : 195−198℃ NMR (CDCl3,δ) : 1.27 (3H,t,J=7Hz), 2.83 (2H,q,J=7
Hz), 5.49 (2H,s),6.29 (1H,d,J=8Hz), 7.03 (1H,t,J=8
Hz), 7.18 (1H,t,J=8Hz), 7.42(1H,d,J=8Hz), 7.50 (1
H,d,J=8Hz), 7.63 (1H,d,J=8Hz), 7.77 (1H,s) (36) １−（２−クロロベンジル）−２−プロピオニル
−３−プロピルインドール−６−カルボキサミド mp : 165−167℃ NMR (CDCl3,δ) : 1.05 (3H,t,J=7Hz), 1.13 (3H,t,J=7
Hz), 1.76 (2H,m),2.93 (2H,q,J=7Hz), 3.08 (2H,m),
5.70 (2H,s), 6.23 (1H,d,J=8Hz),6.97 (1H,t,J=8Hz),
7.12 (1H,t,J=8Hz), 7.47 (1H,d,J=8Hz), 7.53 (1H,d,J
=8Hz), 7.74 (1H,s), 7.76 (1H,d,J=8Hz)(35) 2-chloro-1- (2-chlorobenzyl) -3-ethylindole-6-carboxamide mp: 195-198 ° C. NMR (CDCl3 , δ): 1.27 (3H, t, J = 7 Hz) ), 2.83 (2H, q, J = 7
Hz), 5.49 (2H, s), 6.29 (1H, d, J = 8Hz), 7.03 (1H, t, J = 8
Hz), 7.18 (1H, t, J = 8Hz), 7.42 (1H, d, J = 8Hz), 7.50 (1
(H, d, J = 8Hz), 7.63 (1H, d, J = 8Hz), 7.77 (1H, s) (36) 1- (2-chlorobenzyl) -2-propionyl-3-propylindole-6-carboxamide mp: 165-167 ° C NMR (CDCl3 , δ): 1.05 (3H, t, J = 7Hz), 1.13 (3H, t, J = 7
Hz), 1.76 (2H, m), 2.93 (2H, q, J = 7Hz), 3.08 (2H, m),
5.70 (2H, s), 6.23 (1H, d, J = 8Hz), 6.97 (1H, t, J = 8Hz),
7.12 (1H, t, J = 8Hz), 7.47 (1H, d, J = 8Hz), 7.53 (1H, d, J
= 8Hz), 7.74 (1H, s), 7.76 (1H, d, J = 8Hz)
【０３５９】(37) １−（２−クロロベンジル）−２−
イソブチリル−３−プロピルインドール−６−カルボキ
サミド mp : 159−160.5℃ NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.12 (6H,d,J=7
Hz), 1.76 (2H,m),3.04 (2H,m), 3.36 (1H,m), 5.66 (2
H,s), 6.29 (1H,d,J=8Hz), 6.99(1H,t,J=8Hz), 7.14 (1
H,t,J=8Hz), 7.38 (1H,d,J=8Hz), 7.56 (1H,d,J=8Hz),
7.76 (1H,d,J=8Hz), 7.77 (1H,s) (38) １−（２−クロロベンジル）−３−（３−オキソ
−１−ブテニル）インドール−６−カルボキサミド mp : 248−250℃ NMR (DMSO-d6,δ) : 2.30 (3H,s), 5.61 (2H,s), 6.74
(1H,d,J=8Hz), 6.75(1H,d,J=15Hz), 7.2-7.4 (3H,m),
7.54 (1H,d,J=8Hz), 7.77 (1H,d,J=8Hz), 7.80 (1H,d,J
=15Hz), 7.98 (1H,br s), 8.04 (1H,d,J=8Hz),8.11 (1
H,s), 8.14 (1H,s)(37) 1- (2-chlorobenzyl) -2-
Isobutyryl-3-propylindole-6-carboxamide mp: 159-160.5 ° C NMR (CDCl3 , δ): 1.03 (3H, t, J = 7Hz), 1.12 (6H, d, J = 7
Hz), 1.76 (2H, m), 3.04 (2H, m), 3.36 (1H, m), 5.66 (2
H, s), 6.29 (1H, d, J = 8Hz), 6.99 (1H, t, J = 8Hz), 7.14 (1
H, t, J = 8Hz), 7.38 (1H, d, J = 8Hz), 7.56 (1H, d, J = 8Hz),
7.76 (1H, d, J = 8Hz), 7.77 (1H, s) (38) 1- (2-chlorobenzyl) -3- (3-oxo-1-butenyl) indole-6-carboxamide mp: 248-250 ° C NMR (DMSO-d6 , δ): 2.30 (3H, s), 5.61 (2H, s), 6.74
(1H, d, J = 8Hz), 6.75 (1H, d, J = 15Hz), 7.2-7.4 (3H, m),
7.54 (1H, d, J = 8Hz), 7.77 (1H, d, J = 8Hz), 7.80 (1H, d, J
= 15Hz), 7.98 (1H, brs), 8.04 (1H, d, J = 8Hz), 8.11 (1
H, s), 8.14 (1H, s)
【０３６０】(39) ４−（２−クロロベンジル）−３−
オキソ−１,２,３,４−テトラヒドロシクロペンタ
［ｂ］インドール−６−カルボキサミド mp : 289℃（分解） NMR (DMSO-d6,δ) : 2.95 (2H,m), 3.10 (2H,m), 5.67
(2H,s), 6.37 (1H,d,J=8Hz), 7.16 (1H,t,J=8Hz), 7.28
(1H,t,J=8Hz), 7.40 (1H,br s),7.53 (1H,d,J=8Hz),
7.74 (1H,d,J=8Hz), 7.88 (1H,d,J=8Hz), 8.01(1H,br
s), 8.07 (1H,s) (40) ４−（６−クロロ−３,４−メチレンジオキシベン
ジル）−３−オキソ−１,２,３,４−テトラヒドロシク
ロペンタ［ｂ］インドール−６−カルボキサミド mp : 282℃（分解） NMR (DMSO-d6,δ) : 2.98 (2H,m), 3.09 (2H,m), 5.54
(2H,s), 5.97 (2H,s),5.98 (1H,s), 7.17 (1H,s), 7.43
(1H,br s), 7.71 (1H,d,J=8Hz), 7.86(1H,d,J=8Hz),
8.03 (1H,br s), 8.05 (1H,s)(39) 4- (2-chlorobenzyl) -3-
Oxo-1,2,3,4-tetrahydrocyclopenta [b] indole-6-carboxamide mp: 289 ° C. (decomposition) NMR (DMSO-d6 , δ): 2.95 (2H, m), 3.10 (2H, m ), 5.67
(2H, s), 6.37 (1H, d, J = 8Hz), 7.16 (1H, t, J = 8Hz), 7.28
(1H, t, J = 8Hz), 7.40 (1H, br s), 7.53 (1H, d, J = 8Hz),
7.74 (1H, d, J = 8Hz), 7.88 (1H, d, J = 8Hz), 8.01 (1H, br
s), 8.07 (1H, s) (40) 4- (6-Chloro-3,4-methylenedioxybenzyl) -3-oxo-1,2,3,4-tetrahydrocyclopenta [b] indole-6 -Carboxamide mp: 282 ° C (decomposition) NMR (DMSO-d6 , δ): 2.98 (2H, m), 3.09 (2H, m), 5.54
(2H, s), 5.97 (2H, s), 5.98 (1H, s), 7.17 (1H, s), 7.43
(1H, brs), 7.71 (1H, d, J = 8Hz), 7.86 (1H, d, J = 8Hz),
8.03 (1H, br s), 8.05 (1H, s)
【０３６１】(41) １−［２−クロロ−４−（Ｎ−フェ
ニルスルホニルカルバモイル）ベンジル］−３−イソブ
チリル−２−プロピルインドール−６−カルボキサミド mp : 147−150℃ NMR (DMSO-d6,δ) : 0.88 (3H,t,J=7Hz), 1.18 (6H,d,J
=7Hz), 1.45 (2H,sextet,J=7Hz), 2.98-3.03 (2H,m),
3.55 (1H,septet,J=7Hz), 5.68(2H,s), 6.27 (1H,d,J=8
Hz), 7.28 (1H,s), 7.60-7.64 (3H,m), 7.69(1H,dd,J=
2, 8Hz), 7.80 (1H,d,J=8Hz), 7.92-7.96 (4H,m), 8.06
(1H,s)[0361] (41) 1- [2-chloro-4-(N-phenyl-sulfonylcarbamoyl) benzyl] -3-isobutyryl-2-propyl-indole-6-carboxamide mp: 147-150 ℃ NMR (DMSO- d 6, δ): 0.88 (3H, t, J = 7Hz), 1.18 (6H, d, J
= 7Hz), 1.45 (2H, sextet, J = 7Hz), 2.98-3.03 (2H, m),
3.55 (1H, septet, J = 7Hz), 5.68 (2H, s), 6.27 (1H, d, J = 8
Hz), 7.28 (1H, s), 7.60-7.64 (3H, m), 7.69 (1H, dd, J =
2, 8Hz), 7.80 (1H, d, J = 8Hz), 7.92-7.96 (4H, m), 8.06
(1H, s)
【０３６２】製造例129 製造例59と同様にして、下記(1)〜(5)に記載の化合物を
製造した。 (1) １−（６−クロロ−３,４−メチレンジオキシベン
ジル）−３−メトキシアセチル−２−プロピルインドー
ル−６−カルボキサミド (2) １−（２−クロロベンジル）−３−エトキシアセチ
ル−２−プロピルインドール−６−カルボキサミド NMR (DMSO-d6,δ) : 0.93 (3H,t,J=7Hz), 1.18 (3H,t,J
=7Hz), 1.46 (2H,sextet,J=7Hz), 3.03 (3H,t,J=7Hz),
3.62 (2H,q,J=7Hz), 4.74 (2H,s),5.63 (2H,s), 6.22
(1H,d,J=8Hz), 7.17 (1H,t,J=8Hz), 7.30 (1H,s),7.33
(1H,t,J=8Hz), 7.58 (1H,d,J=8Hz), 7.80 (1H,d,J=8H
z), 7.92 (1H,d,J=8Hz), 7.94 (1H,s), 8.00 (1H,s)Production Example 129 The following compounds (1) to (5) were produced in the same manner as in Production Example 59. (1) 1- (6-chloro-3,4-methylenedioxybenzyl) -3-methoxyacetyl-2-propylindole-6-carboxamide (2) 1- (2-chlorobenzyl) -3-ethoxyacetyl- 2-propyl-indole-6-carboxamideNMR (DMSO-d 6, δ ): 0.93 (3H, t, J = 7Hz), 1.18 (3H, t, J
= 7Hz), 1.46 (2H, sextet, J = 7Hz), 3.03 (3H, t, J = 7Hz),
3.62 (2H, q, J = 7Hz), 4.74 (2H, s), 5.63 (2H, s), 6.22
(1H, d, J = 8Hz), 7.17 (1H, t, J = 8Hz), 7.30 (1H, s), 7.33
(1H, t, J = 8Hz), 7.58 (1H, d, J = 8Hz), 7.80 (1H, d, J = 8H)
z), 7.92 (1H, d, J = 8Hz), 7.94 (1H, s), 8.00 (1H, s)
【０３６３】(3) １−（２−クロロベンジル）−３−イ
ソブチリル−２−プロピルインドール−６−イルアセト
アミド mp : 146−148℃ IR (KBr) : 1715, 1650 cm-1 NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.57-1.67 (2H,m), 3.02-3.08 (2H,m), 3.51-3.60
(1H,m), 3.66 (2H,s), 5.45 (2H,s),6.29 (1H,d,J=7.5
Hz), 7.04-7.09 (2H,m), 7.21 (2H,t,J=7.5Hz), 7.47(1
H,d,J=7.5Hz), 7.93 (1H,d,J=7.5Hz) MASS (m/z) : 411 (M++1), 74 (bp) (4) １−（６−クロロ−３,４−メチレンジオキシベン
ジル）−３−イソブチリル−２−プロピルインドール−
６−イルアセトアミド mp : 136−138℃ IR (KBr) : 1655, 1505 cm-1 NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.29 (6H,d,J=7
Hz), 1.55-1.67 (2H,m), 3.01-3.07 (2H,m), 3.50-3.58
(1H,m), 3.69 (2H,s), 5.33 (2H,s),5.75 (1H,s), 5.9
0 (2H,s), 6.92 (1H,s), 7.09 (1H,s), 7.19 (1H,d,J=
7.5Hz), 7.91 (1H,d,J=7.5Hz) MASS (m/z) : 455 (M++1), 74 (bp)(3) 1- (2-chlorobenzyl) -3-isobutyryl-2-propylindole-6-ylacetamide mp: 146-148 ° C IR (KBr): 1715, 1650 cm-1 NMR (CDCl3 , δ): 1.01 (3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.57-1.67 (2H, m), 3.02-3.08 (2H, m), 3.51-3.60
(1H, m), 3.66 (2H, s), 5.45 (2H, s), 6.29 (1H, d, J = 7.5
Hz), 7.04-7.09 (2H, m), 7.21 (2H, t, J = 7.5Hz), 7.47 (1
H, d, J = 7.5Hz), 7.93 (1H, d, J = 7.5Hz) MASS (m / z): 411 (M+ +1), 74 (bp) (4) 1- (6-chloro- 3,4-methylenedioxybenzyl) -3-isobutyryl-2-propylindole-
6-ylacetamide mp: 136-138 ° C IR (KBr): 1655, 1505 cm-1 NMR (CDCl3 , δ): 1.04 (3H, t, J = 7Hz), 1.29 (6H, d, J = 7
Hz), 1.55-1.67 (2H, m), 3.01-3.07 (2H, m), 3.50-3.58
(1H, m), 3.69 (2H, s), 5.33 (2H, s), 5.75 (1H, s), 5.9
0 (2H, s), 6.92 (1H, s), 7.09 (1H, s), 7.19 (1H, d, J =
7.5Hz), 7.91 (1H, d, J = 7.5Hz) MASS (m / z): 455 (M+ +1), 74 (bp)
【０３６４】(5) １−（２−クロロベンジル）−３−ニ
トロ−２−プロピルインドール−６−カルボキサミド NMR (DMSO-d6,δ) : 0.95 (3H,t,J=7Hz), 1.54 (2H,sex
tet,J=7Hz), 3.13-3.17 (2H,m), 5.72 (2H,s), 6.44 (1
H,d,J=8Hz), 7.20 (1H,t,J=8Hz),7.36 (1H,t,J=8Hz),
7.42 (1H,s), 7.60 (1H,d,J=8Hz), 7.96 (1H,d,J=8Hz),
8.03 (1H,s), 8.10 (1H,s), 8.22 (1H,d,J=8Hz)(5) 1- (2-chlorobenzyl) -3-nitro-2-propylindole-6-carboxamide NMR (DMSO-d6 , δ): 0.95 (3H, t, J = 7 Hz), 1.54 ( 2H, sex
tet, J = 7Hz), 3.13-3.17 (2H, m), 5.72 (2H, s), 6.44 (1
H, d, J = 8Hz), 7.20 (1H, t, J = 8Hz), 7.36 (1H, t, J = 8Hz),
7.42 (1H, s), 7.60 (1H, d, J = 8Hz), 7.96 (1H, d, J = 8Hz),
8.03 (1H, s), 8.10 (1H, s), 8.22 (1H, d, J = 8Hz)
【０３６５】製造例130 製造例79と同様にして、下記(1)〜(13)に記載の化合物
を製造した。 (1) １−（４−クロロ−２−フルオロベンジル）−３−
メトキシアセチル−２−プロピルインドール−６−カル
ボキサミド mp : 192−193℃ NMR (DMSO-d6,δ) : 0.94 (3H,t,J=7Hz), 1.44 (2H,sex
tet,J=7Hz), 3.09(2H,t,J=7Hz), 3.41 (3H,s), 4.69 (2
H,s), 5.64 (2H,s), 6.50 (1H,t,J=8Hz), 7.18 (1H,dd,
J=2, 8Hz), 7.33 (1H,s), 7.55 (1H,dd,J=2, 8Hz),7.79
(1H,d,J=8Hz), 7.89 (1H,d,J=8Hz), 7.92 (1H,s), 8.0
6 (1H,s) (2) １−（２,４−ジクロロベンジル）−３−メトキシ
アセチル−２−プロピルインドール−６−カルボキサミ
ド mp : 203−205℃ NMR (DMSO-d6,δ) : 0.94 (3H,t,J=7Hz), 1.98 (2H,sex
tet,J=7Hz), 3.04(2H,t,J=7Hz), 3.42 (3H,s), 4.71 (2
H,s), 5.60 (2H,s), 6.20 (1H,d,J=8Hz), 7.27 (1H,dd,
J=2, 8Hz), 7.32 (1H,s), 7.77 (1H,d,J=2Hz),7.82 (1
H,d,J=8Hz), 7.92 (1H,d,J=8Hz), 7.94 (1H,s), 7.98
(1H,s)Production Example 130 The following compounds (1) to (13) were produced in the same manner as in Production Example 79. (1) 1- (4-chloro-2-fluorobenzyl) -3-
Methoxyacetyl-2-propylindole-6-carboxamide mp: 192-193 ° C NMR (DMSO-d6 , δ): 0.94 (3H, t, J = 7Hz), 1.44 (2H, sex
tet, J = 7Hz), 3.09 (2H, t, J = 7Hz), 3.41 (3H, s), 4.69 (2
H, s), 5.64 (2H, s), 6.50 (1H, t, J = 8Hz), 7.18 (1H, dd,
J = 2,8Hz), 7.33 (1H, s), 7.55 (1H, dd, J = 2,8Hz), 7.79
(1H, d, J = 8Hz), 7.89 (1H, d, J = 8Hz), 7.92 (1H, s), 8.0
6 (1H, s) (2) 1- (2,4-dichlorobenzyl) -3-methoxyacetyl-2-propylindole-6-carboxamide mp: 203-205 ° C NMR (DMSO-d6 , δ): 0.94 (3H, t, J = 7Hz), 1.98 (2H, sex
tet, J = 7Hz), 3.04 (2H, t, J = 7Hz), 3.42 (3H, s), 4.71 (2
H, s), 5.60 (2H, s), 6.20 (1H, d, J = 8Hz), 7.27 (1H, dd,
J = 2,8Hz), 7.32 (1H, s), 7.77 (1H, d, J = 2Hz), 7.82 (1
(H, d, J = 8Hz), 7.92 (1H, d, J = 8Hz), 7.94 (1H, s), 7.98
(1H, s)
【０３６６】(3) １−（４−ブロモ−２−クロロベンジ
ル）−３−メトキシアセチル−２−プロピルインドール
−６−カルボキサミド mp : 178−180℃ NMR (DMSO-d6,δ) : 0.94 (3H,t,J=7Hz), 1.48 (2H,sex
tet,J=7Hz), 3.04(2H,t,J=7Hz), 3.42 (3H,s), 4.68 (2
H,s), 5.57 (2H,s), 6.13 (1H,d,J=8Hz), 7.30 (1H,s),
7.38 (1H,dd,J=2, 8Hz), 7.80 (1H,d,J=8Hz),7.86 (1
H,d,J=2Hz), 7.90 (1H,d,J=8Hz), 7.93 (1H,s), 7.97
(1H,s) (4) １−（４−ブロモ−２−フルオロベンジル）−３−
メトキシアセチル−２−プロピルインドール−６−カル
ボキサミド mp : 197−199℃ NMR (DMSO-d6,δ) : 0.94 (3H,t,J=7Hz), 1.48 (2H,sex
tet,J=7Hz), 3.09(2H,t,J=7Hz), 3.40 (3H,s), 4.67 (2
H,s), 5.62 (2H,s), 6.43 (1H,d,J=8Hz), 7.28 (1H,dd,
J=2, 8Hz), 7.65 (1H,dd,J=2, 8Hz), 7.78 (1H,d,J=8H
z), 7.90 (1H,d,J=8Hz), 7.92 (1H,s), 8.05 (1H,s)(3) 1- (4-bromo-2-chlorobenzyl) -3-methoxyacetyl-2-propylindole-6-carboxamide mp: 178-180 ° C. NMR (DMSO-d6 , δ): 0.94 ( 3H, t, J = 7Hz), 1.48 (2H, sex
tet, J = 7Hz), 3.04 (2H, t, J = 7Hz), 3.42 (3H, s), 4.68 (2
H, s), 5.57 (2H, s), 6.13 (1H, d, J = 8Hz), 7.30 (1H, s),
7.38 (1H, dd, J = 2,8Hz), 7.80 (1H, d, J = 8Hz), 7.86 (1
(H, d, J = 2Hz), 7.90 (1H, d, J = 8Hz), 7.93 (1H, s), 7.97
(1H, s) (4) 1- (4-bromo-2-fluorobenzyl) -3-
Methoxyacetyl-2-propylindole-6-carboxamide mp: 197-199 ° C NMR (DMSO-d6 , δ): 0.94 (3H, t, J = 7Hz), 1.48 (2H, sex
tet, J = 7Hz), 3.09 (2H, t, J = 7Hz), 3.40 (3H, s), 4.67 (2
H, s), 5.62 (2H, s), 6.43 (1H, d, J = 8Hz), 7.28 (1H, dd,
J = 2, 8Hz), 7.65 (1H, dd, J = 2,8Hz), 7.78 (1H, d, J = 8H
z), 7.90 (1H, d, J = 8Hz), 7.92 (1H, s), 8.05 (1H, s)
【０３６７】(5) １−（２−クロロ−４−フルオロベン
ジル）−３−メトキシアセチル−２−プロピルインドー
ル−６−カルボキサミド mp : 174−176℃ NMR (DMSO-d6,δ) : 0.93 (3H,t,J=7Hz), 1.48 (2H,sex
tet,J=7Hz), 3.04(2H,t,J=7Hz), 3.42 (3H,s), 4.70 (2
H,s), 5.58 (2H,s), 6.25 (1H,d,J=8Hz), 7.06 (1H,dt,
J=2, 8Hz), 7.32 (1H,s), 7.50 (1H,dd,J=2, 7Hz),7.80
(1H,d,J=8Hz), 7.92 (1H,d,J=8Hz), 7.94 (1H,s), 8.0
0 (1H,s) (6) １−（ベンゾ［ｂ］チオフェン−５−イルメチル）
−３−メトキシアセチル−２−プロピルインドール−６
−カルボキサミド mp : 197−199℃（分解） NMR (DMSO-d6,δ) : 0.92 (3H,t,J=7Hz), 1.48 (2H,sex
tet,J=7Hz), 3.14(2H,t,J=7Hz), 3.42 (3H,s), 4.72 (2
H,s), 5.74 (2H,s), 7.10 (1H,d,J=8Hz), 7.28 (1H,s),
7.38 (1H,d,J=5Hz), 7.44 (1H,s), 7.75 (1H,d,J=5H
z), 7.78 (1H,d,J=8Hz), 7.88 (1H,d,J=8Hz), 7.92 (1
H,s), 7.96(1H,d,J=8Hz), 8.12 (1H,s)(5) 1- (2-chloro-4-fluorobenzyl) -3-methoxyacetyl-2-propylindole-6-carboxamide mp: 174-176 ° C NMR (DMSO-d6 , δ): 0.93 ( 3H, t, J = 7Hz), 1.48 (2H, sex
tet, J = 7Hz), 3.04 (2H, t, J = 7Hz), 3.42 (3H, s), 4.70 (2
H, s), 5.58 (2H, s), 6.25 (1H, d, J = 8Hz), 7.06 (1H, dt,
J = 2,8Hz), 7.32 (1H, s), 7.50 (1H, dd, J = 2,7Hz), 7.80
(1H, d, J = 8Hz), 7.92 (1H, d, J = 8Hz), 7.94 (1H, s), 8.0
0 (1H, s) (6) 1- (benzo [b] thiophen-5-ylmethyl)
-3-methoxyacetyl-2-propylindole-6
-Carboxamide mp: 197-199 ° C (decomposition) NMR (DMSO-d6 , δ): 0.92 (3H, t, J = 7Hz), 1.48 (2H, sex
tet, J = 7Hz), 3.14 (2H, t, J = 7Hz), 3.42 (3H, s), 4.72 (2
H, s), 5.74 (2H, s), 7.10 (1H, d, J = 8Hz), 7.28 (1H, s),
7.38 (1H, d, J = 5H), 7.44 (1H, s), 7.75 (1H, d, J = 5H)
z), 7.78 (1H, d, J = 8Hz), 7.88 (1H, d, J = 8Hz), 7.92 (1
H, s), 7.96 (1H, d, J = 8Hz), 8.12 (1H, s)
【０３６８】(7) １−（２,４−ジクロロベンジル）−
３−イソブチリル−２−プロピルインドール−６−カル
ボン酸メチルエステル NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.31 (6H,d,J=7
Hz), 1.60 (2H,sextet,J=7Hz), 3.06 (2H,t,J=7Hz), 3.
58 (2H,septet,J=7Hz), 3.93(3H,s), 5.46 (2H,s), 6.1
6 (1H,d,J=8Hz), 7.04 (1H,d,J=8Hz), 7.50(1H,s), 7.9
0 (1H,s), 7.96 (2H,s) (8) ３−イソブチリル−２−プロピル−１−（３−ピリ
ジルメチル）インドール−６−カルボン酸メチルエステ
ル NMR (CDCl3,δ) : 1.02 (3H,t,J=7Hz), 1.30 (6H,d,J=7
Hz), 1.60 (2H,sextet,J=7Hz), 3.12 (2H,t,J=7Hz), 3.
56 (2H,septet,J=7Hz), 3.92(3H,s), 5.48 (2H,s), 7.1
4-7.23 (2H,m), 7.92-7.95 (2H,m), 7.98 (1H,s), 8.42
(1H,d,J=2Hz), 8.54 (1H,d,J=5Hz)(7) 1- (2,4-dichlorobenzyl)-
3-isobutyryl-2-propylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.02 (3H, t, J = 7 Hz), 1.31 (6H, d, J = 7)
Hz), 1.60 (2H, sextet, J = 7Hz), 3.06 (2H, t, J = 7Hz), 3.
58 (2H, septet, J = 7Hz), 3.93 (3H, s), 5.46 (2H, s), 6.1
6 (1H, d, J = 8Hz), 7.04 (1H, d, J = 8Hz), 7.50 (1H, s), 7.9
0 (1H, s), 7.96 (2H, s) (8) 3-isobutyryl-2-propyl-1- (3-pyridylmethyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.02 ( 3H, t, J = 7Hz), 1.30 (6H, d, J = 7
Hz), 1.60 (2H, sextet, J = 7Hz), 3.12 (2H, t, J = 7Hz), 3.
56 (2H, septet, J = 7Hz), 3.92 (3H, s), 5.48 (2H, s), 7.1
4-7.23 (2H, m), 7.92-7.95 (2H, m), 7.98 (1H, s), 8.42
(1H, d, J = 2Hz), 8.54 (1H, d, J = 5Hz)
【０３６９】(9) ３−イソブチリル−２−プロピル−１
−（１−ナフチルメチル）インドール−６−カルボン酸
メチルエステル NMR (CDCl3,δ) : 0.97 (3H,t,J=7Hz), 1.34 (6H,d,J=7
Hz), 1.64 (2H,sextet,J=7Hz), 3.04-3.10 (2H,m), 3.6
3 (1H,septet,J=7Hz), 3.84 (3H,s), 5.92 (2H,s), 6.2
8 (1H,d,J=8Hz), 7.22 (1H,t,J=8Hz), 7.62 (1H,t,J=8H
z), 7.69 (1H,t,J=8Hz), 7.77 (1H,d,J=8Hz), 7.77 (2
H,s), 7.92(1H,s) (10) ３−イソブチリル−２−プロピル−１−（２−ナ
フチルメチル）インドール−６−カルボン酸メチルエス
テル NMR (CDCl3,δ) : 1.00 (3H,t,J=7Hz), 1.32 (6H,d,J=7
Hz), 1.55-1.68 (2H,m), 3.13-3.18 (2H,m), 3.60 (1H,
septet,J=7Hz), 3.88 (3H,s), 5.62(2H,s), 7.17 (1H,
d,J=8Hz), 7.29 (2H,s), 7.42-7.48 (2H,m), 7.64-7.68
(1H,m), 7.80 (2H,d,J=2Hz), 7.96 (2H,s), 8.04 (1H,
s)(9) 3-isobutyryl-2-propyl-1
- (1-naphthylmethyl) indole-6-carboxylic acid methyl esterNMR (CDCl 3, δ): 0.97 (3H, t, J = 7Hz), 1.34 (6H, d, J = 7
Hz), 1.64 (2H, sextet, J = 7Hz), 3.04-3.10 (2H, m), 3.6
3 (1H, septet, J = 7Hz), 3.84 (3H, s), 5.92 (2H, s), 6.2
8 (1H, d, J = 8Hz), 7.22 (1H, t, J = 8Hz), 7.62 (1H, t, J = 8H)
z), 7.69 (1H, t, J = 8Hz), 7.77 (1H, d, J = 8Hz), 7.77 (2
H, s), 7.92 (1H, s) (10) 3-isobutyryl-2-propyl-1- (2-naphthylmethyl) indole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.00 (3H, t, J = 7Hz), 1.32 (6H, d, J = 7
Hz), 1.55-1.68 (2H, m), 3.13-3.18 (2H, m), 3.60 (1H,
septet, J = 7Hz), 3.88 (3H, s), 5.62 (2H, s), 7.17 (1H,
d, J = 8Hz), 7.29 (2H, s), 7.42-7.48 (2H, m), 7.64-7.68
(1H, m), 7.80 (2H, d, J = 2Hz), 7.96 (2H, s), 8.04 (1H,
s)
【０３７０】(11) １−（６−クロロ−３,４−メチレン
ジオキシベンジル）−３−メトキシアセチル−２−プロ
ピルインドール−６−カルボン酸メチルエステル NMR (CDCl3,δ) : 1.04 (3H,t,J=7Hz), 1.56-1.72 (2H,
m), 3.06-3.13 (2H,m), 3.58 (3H,s), 3.93 (3H,s), 4.
73 (2H,s), 5.40 (2H,s), 5.70 (1H,s), 5.88 (2H,s),
6.92 (1H,s), 7.83 (1H,d,J=8Hz), 7.96 (1H,s),7.98
(1H,d,J=8Hz) (12) １−（２−クロロベンジル）−３−エトキシアセ
チル−２−プロピルインドール−６−カルボン酸メチル
エステル NMR (CDCl3,δ) : 1.03 (3H,t,J=7Hz), 1.34 (3H,t,J=7
Hz), 1.56-1.70 (2H,m), 3.10 (3H,t,J=7Hz), 3.77 (2
H,q,J=7Hz), 3.92 (3H,s), 4.79 (2H,s), 5.52 (2H,s),
6.24 (1H,d,J=8Hz), 7.03 (1H,t,J=8Hz), 7.22 (1H,t,
J=8Hz), 7.46 (1H,d,J=8Hz), 7.85 (1H,d,J=8Hz), 7.92
(1H,s), 7.98(1H,d,J=8Hz)(11) 1- (6-chloro-3,4-methylenedioxybenzyl) -3-methoxyacetyl-2-propylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.04 (3H , t, J = 7Hz), 1.56-1.72 (2H,
m), 3.06-3.13 (2H, m), 3.58 (3H, s), 3.93 (3H, s), 4.
73 (2H, s), 5.40 (2H, s), 5.70 (1H, s), 5.88 (2H, s),
6.92 (1H, s), 7.83 (1H, d, J = 8Hz), 7.96 (1H, s), 7.98
(1H, d, J = 8 Hz) (12) 1- (2-chlorobenzyl) -3-ethoxyacetyl-2-propylindole-6-carboxylic acid methyl ester NMR (CDCl3 , δ): 1.03 (3H, t , J = 7Hz), 1.34 (3H, t, J = 7
Hz), 1.56-1.70 (2H, m), 3.10 (3H, t, J = 7Hz), 3.77 (2
(H, q, J = 7Hz), 3.92 (3H, s), 4.79 (2H, s), 5.52 (2H, s),
6.24 (1H, d, J = 8Hz), 7.03 (1H, t, J = 8Hz), 7.22 (1H, t,
J = 8Hz), 7.46 (1H, d, J = 8Hz), 7.85 (1H, d, J = 8Hz), 7.92
(1H, s), 7.98 (1H, d, J = 8Hz)
【０３７１】(13) １−（２−クロロ−４−メトキシカ
ルボニルベンジル）−３−イソブチリル−２−プロピル
インドール−６−カルボキサミド NMR (CDCl3,δ) : 1.01 (3H,t,J=7Hz), 1.32 (6H,d,J=7
Hz), 1.60 (2H,sextet,J=7Hz), 3.02-3.06 (2H,m), 3.5
6 (1H,septet,J=7Hz), 3.90 (3H,s), 5.53 (2H,s), 6.2
8 (1H,d,J=8Hz), 7.63 (1H,d,J=8Hz), 7.69 (1H,d,J=8H
z), 7.82 (1H,s), 7.98 (1H,d,J=8Hz), 8.14 (1H,s)(13) 1- (2-chloro-4-methoxycarbonylbenzyl) -3-isobutyryl-2-propylindole-6-carboxamide NMR (CDCl3 , δ): 1.01 (3H, t, J = 7 Hz) , 1.32 (6H, d, J = 7
Hz), 1.60 (2H, sextet, J = 7Hz), 3.02-3.06 (2H, m), 3.5
6 (1H, septet, J = 7Hz), 3.90 (3H, s), 5.53 (2H, s), 6.2
8 (1H, d, J = 8Hz), 7.63 (1H, d, J = 8Hz), 7.69 (1H, d, J = 8H
z), 7.82 (1H, s), 7.98 (1H, d, J = 8Hz), 8.14 (1H, s)
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 31/44 Ａ６１Ｋ 31/44 31/535 31/535 // Ｃ０７Ｄ 209/08 Ｃ０７Ｄ 209/08 209/10 209/10 209/12 209/12 209/14 209/14 209/18 209/18 209/70 209/70 209/88 209/88 401/06 ２０９ 401/06 ２０９ 403/04 ２０９ 403/04 ２０９ 405/04 ２０９ 405/04 ２０９ 409/06 ２０９ 409/06 ２０９ 417/06 ２０９ 417/06 ２０９──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl.6 Identification code Agency reference number FI Technical display location A61K 31/44 A61K 31/44 31/535 31/535 // C07D 209/08 C07D 209/08 209 / 10 209/10 209/12 209/12 209/14 209/14 209/18 209/18 209/70 209/70 209/88 209/88 401/06 209 401/06 209 403/04 209 403/04 209 405/04 209 405/04 209 409/06 209 409/06 209 417/06 209 417/06 209
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU1188 | 1996-07-23 | ||
| AUPO1188AAUPO118896A0 (en) | 1996-07-23 | 1996-07-23 | New use |
| Publication Number | Publication Date |
|---|---|
| JPH1067682Atrue JPH1067682A (en) | 1998-03-10 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP19161897APendingJPH1067682A (en) | 1996-07-23 | 1997-07-16 | New use |
| Country | Link |
|---|---|
| JP (1) | JPH1067682A (en) |
| AU (1) | AUPO118896A0 (en) |
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| WO2001032621A1 (en)* | 1999-10-29 | 2001-05-10 | Wakunaga Pharmaceutical Co., Ltd. | Novel indole derivatives and drugs containing the same as the active ingredient |
| WO2001043746A1 (en)* | 1999-12-14 | 2001-06-21 | Nippon Shinyaku Co., Ltd. | Medicinal composition |
| EP1891951A1 (en) | 2001-07-25 | 2008-02-27 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
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| US7141574B2 (en) | 2001-07-25 | 2006-11-28 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| EA007722B1 (en)* | 2001-07-25 | 2006-12-29 | Бёрингер Ингельхайм (Канада) Лтд. | Viral polymerase inhibitors |
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| US7157486B2 (en) | 2001-07-25 | 2007-01-02 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| EP1891950A1 (en)* | 2001-07-25 | 2008-02-27 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| WO2003010141A3 (en)* | 2001-07-25 | 2003-05-30 | Boehringer Ingelheim Ca Ltd | Hepatitis c virus polymerase inhibitors with a heterobicyclic structure |
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| US7576079B2 (en) | 2001-07-25 | 2009-08-18 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
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| EP2335700A1 (en) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C virus polymerase inhibitors with a heterobicylic structure |
| HRP20040072B1 (en)* | 2001-07-25 | 2012-01-31 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| CN1558759B (en) | 2001-07-25 | 2012-01-25 | 贝林格尔·英格海姆加拿大有限公司 | Viral polymerase inhibitors |
| US7098241B2 (en) | 2002-12-16 | 2006-08-29 | Hoffmann-La Roche Inc. | Thiophene hydroxamic acid derivatives |
| US7582770B2 (en) | 2004-02-20 | 2009-09-01 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
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