SYNTHESIS : (from 5-methoxytryptamine) A solution of 0.95 g offree-base 5-methoxytryptamine was dissolved in 10 mL warm IPA and,after returning to room temperature, treated first with 2.8 mLdiisopropylethylamine followed by 1.2 mL bromoethane. After 3 days,TLC showed considerable starting material, so there was added anadditional 2.8 g of the amine and 1.2 g of the bromide and theroom-temperature stirring continued for an additional 3 days. Thevolatiles were removed under vacuum, and the residue treated with 1.6g acetic anhydride, and heated on the steam bath for 20 min. Theexcess anhydride was destroyed by the addition of 3 mL concentratedNH4OH, followed by dilution with 100 mL 0.5 N H2SO4. The aqueous phasewas washed with 3x50 mL CH2Cl2, made basic with 6N NaOH and extractedwith 3x25 mL CH2Cl2. The solvent from the pooled extracts was removedunder vacuum, and the residue distilled at the KugelRohr. A fractionboiling at 190-200 °C at 0.5 mm / Hg providing 0.45 g of a whiteoil. This was dissolved in 2.5 mL IPA, acidified with approximately 8drops of concentrated HCl which produced spontaneouscrystallization. There was added, slowly and with good stirring, 20 mLof anhydrous Et2O to yield beautiful white crystals ofN,N-diethyl-5-methoxytryptamine hydrochloride (5-MeO-DET), weighing0.50 g (35%) and with a mp 190-191 °C. IR (in cm-1): 817, 830, 930,1109, 1185. MS (in m/z): C5H12N+ 86 (100%), C3H8N+ 58 (12%);indolemethylene+ 160 (4%); parent ion 246 (2%).
The pooled extracts of the CH2Cl2 washings of the acidified aqueousphase above gave, upon removal of the solvent under vacuum, a brownishresidue that crystallized. Recrystallization of this from MeOH gave0.44 g of N-ethylmelatonin as a white crystalline solid. IR (in cm-1):790, 829, 929, 1031, 1068,1108, 1182, 1199. MS (in m/z): 173 (100%);indolemethylene+ 160 (67%); parent ion 260 (14%). This amide provedextremely difficult to hydrolyze.
(from 5-methoxyindole) To a well-stirred solution of 1.5 g5-methoxyindole in 15 mL anhydrous Et2O there was added, dropwise overthe course of 30 min, a solution of 1.4 g oxalyl chloride in 15 mLanhydrous Et2O. Stirring was continued for an additional 15 min duringwhich time there was the separation of 5-methoxyindol-3-ylglyoxylchloride as a red crystalline solid. This intermediate was removed byfiltration and washed with Et2O, and was used directly in thefollowing step. This was added in small dabs to 2.0 g anhydrousdiethylamine, cooled and well-stirred. The off-white resulting solidswere suspended in 100 mL 1 N HCl, stirred until it was a loose andcreamy texture, then filtered and washed with H2O. Recrystallizationfrom acetonitrile gave 2.24 g (80%)5-methoxy-N,N-diethylindol-3-ylglyoxylamide as white solids, with a mpof 158-160 °C.
A solution of 2.1 g 5-methoxy-N,N-diethylindol-3-ylglyoxylamide in 35mL anhydrous THF was added, slowly, to 3.2 g LAH in 60 mL THF whichwas well-stirred and held at reflux temperature under an inertatmosphere. After the addition was complete, reflux was maintained foran additional 16 h, the reaction mixture cooled, and the excesshydride destroyed by the cautious addition of wet THF. Aqueous 15%NaOH was added cautiously until the solids had a loose white cottagecheese character to them, and the mobile phase tested basic byexternal damp pH paper. These solids were removed by filtration,washed with first THF and then with MeOH. The filtrate and washingswere combined, dried over anhydrous MgSO4, and the solvent removedunder vacuum. The residue was distilled yielding a fraction boiling at190-200 °C at 0.5 mm / Hg that weighed 1.45 g and was a whiteoil. This was dissolved in 8 mL IPA, acidified with concentrated HCluntil it was acidic to external damp pH paper, and diluted with Et2Oand stirred until crystallization appeared to becomplete. N,N-diethyl-5-methoxytryptamine hydrochloride (5-MeO-DET)was obtained as white crystals, weighing 1.60 g (74%).
DOSAGE : 1 - 3 mg, orally
DURATION : 3 - 4 hrs
QUALITATIVE COMMENTS : (with 2 mg, orally) "My tinnitus isreally out there, and there is no way of getting away fromit. Light-headed in a funny way -- no hypotension, not dizzy -- maybesomething to do with the inner-ear? It is in the head, I am attentive,and I am not comfortable. Three hours into it I am down, and I have abit of wine, and I am aware of it. Am I drunk? Was I drunk earlier? Iwas intoxicated, to be sure.
(with 3 mg, orally) "It hit in a half hour, and the thought that cameto mind was the phrase from my days at college, "Boy, I really feltthat drink!" I may be sloppy, but let me explore the sexual. Wow. Imay be spacey in the head, but my body knows where it is at. The nextday was normal. I don't think I want to do this again."
(with 3 mg, orally) "Effect felt within 20 mins., mainlylight-headedness, almost dizziness. This blocked anything else. Justwanted to stay quiet and hope it would all go away as soon aspossible. During the next hour, lying beside husband (who wasexperiencing the same effect but not minding it as much), I becameaware of another dimension behind the dizziness. I could sense enoughof it to believe that it would have been interesting to explore, butthat there was no way to get through the dizzies, which effectivelyblocked anything else. At approximately the hour and a half totwo-hour point, I felt a faint lessening of the head-fuzzies, andtested it out by walking to the living room. Felt it necessary to walkcarefully. Body felt heavy and mood was rather dark, verging ondepressed. After that, attempted love-making, which wasextraordinarily successful for husband. For myself, there was still areluctance to let down my guard. My back problems had been botheringme quite a bit, during all of this, and even two Bufferins didn't helpas much as I would have liked. It's quite obvious that, if it werepossible to remove the part of the molecule that causes the dizzies,this would be one of the best drugs for erotic stuff imaginable. Andif wishes were horses, etc. Too bad. Would I try this again? And at ahigher dosage? No, and No. "
(10 mgs, smoked with peppermint leaves) "After a few minutes a highfeeling with some dizziness, intense heartbeat, trembling, anxiety,restlessness, cold sweating, paleness and weak belly cramps. Therewere some visions I could not concentrate because of the strongside-effects. I felt sick, went to bed and was very glad when theeffects disappeared after about one and a half hour."
EXTENSIONS AND COMMENTARY : The is one of the most provocativetemptresses I have ever encountered in the tryptamine world. It is acase of having a protégé that you absolutely know will be asuccess if allowed to come to fulfillment, and yet you know thatuncontrolled circumstances will prevent that fulfillment.
Here is a simple, easy to make compound that lies in-between the lowerhomologue, 5-MeO-DMT (active at 10+ milligrams by any parenteralroute) and 5-MeO-DIPT (active at 10+ milligrams orally). The mostrudimentary logical demands, yea, screams, that 5-MeO-DET should beactive at 10+ milligrams, probably also by the oral route. That is theclear potential of this individual. But, at a fraction of this dosage,an unexpected new property is apparent, one that suggestsneurotoxicity, and thus will preclude the achievement of that 10milligram psychedelic potential. There is a light-headedness, avertigo and intoxication, a warning of fragility, that prettyeffectively blocks any exploration into area that might bepsychologically virtuous. This is reinforced by a report I hadreceived from a person who had smoked some 10 milligrams of it. Hisreport is in the qualitative comments above. He described it as a"torture psychedelic."
This is a new and totally unexpected negative activity may well beunique to this particular diethyl material -- it certainly was notreported with either of the immediate homologues, the dimethyl or thediisopropyl. And, as an intriguing corollary, could the unexpectednew activity property that brought the physical concern also be thething that brought the terrific erotic enhancement? Are they tiedtogether as a single new component of action? Or might there be twonew components of action, the scary vertigo and the friendlysexual?
To me, an obvious bridge to help explain this seeming discontinuity,would be the dipropyl analogue, I made the compound, and explored itup to its active levels. It is an easy compound to make, and has beenknown in the scientific literature for may years. My quandary was howto present it in this book. Should I make it a recipe in its ownrights, giving the detailed synthesis and a formal position as anactive tryptamine? But its actions are ambiguous, and not totallypositive, making an argument for its inclusion as a footnote in someother, more interesting recipe. It is this latter route that I havechosen, so here is the 5-MeO-DPT story, both chemical andpharmacological, tucked away in the bigger 5-MeO-DET
CHEMISTRY : To a warm solution of 0.9 g 5-methoxytryptamine in 10 mLisopropanol there was added 2.8 mL diisopropylethylamine and 1.5 mLpropyl iodide, and the mixture was heated on the steam bath for 5h. TLC analysis at this time showed the presence of both the mono- andthe dialkylamines, but there was no indication of the presence ofunreacted 5-methoxytryptamine or of the quaternary salt. After removalof the volatiles under vacuum, a CH2Cl2 solution of the residue wastreated with 1 g acetic anhydride (on the steam bath for 5 min)followed by 2 mL ammonium hydroxide. Extraction of this solution with1 N H2SO4 proved to be almost worthless, as the extracts afterseparation, alkalinification with 6 N NaOH, extraction with CH2Cl2 anddistillation of the residues following removal of the solvent,provided only a few milligrams of the desired product. The product hadremained in the CH2Cl2. The solvent was removed under vacuum, and theresidue partitioned between methanol (containing a small amount ofaqueous NaOH) and hexane. The hexane fraction was concentrated undervacuum to provide 0.54 g of an almost colorless oil which wasdistilled by KugelRohr. A white oil was obtained, boiling at 170-180°C at 0.04 mm / Hg which weighed 0.49 g. This was dissolved in 2.5mL isopropanol and neutralized with 8 drops of concentrated HCl. Thesolution was diluted with 25 mL anhydrous Et2O to provide5-methoxy-N,N-dipropyltryptamine hydrochloride as a white crystallinesalt. This was removed by filtration, washed with Et2O, air dried toconstant weight, and weighed 0.54 g. The mp was 193-194 °C. IR (incm-1): 811, 828, 929, 1079, 1103, 1186. MS (in m/z): C7H16N+ 114(100%); methoxyindolemethylene+ 160 (13%); parent ion 274 (3%).
QUALITATIVE COMMENTS : (with 4.0 mg, orally) "Within the hourthere is something and after another hour there is nothing. Happy togo on up."
(with 6.0 mg, orally) "I am up above background for sure. Maybe to a++, erotic maybe, and not too much light-headedness. It iscomfortable. Completely out before the fourth hour."
(with 8.4 mg, orally) "Aware in 12 minutes, some head noises at 20minutes. These noises are reminiscent of the 5-MeO-DET in that theywere "bells" which were bad and the underlying "turn-on" which wasgood. But the "bells" were outweighing the "turn-on." Let's ride itout but then, for that matter, what choice is there! At the 25 minutepoint the turn-on now outweighs the bell noise. But these keepalternating. Pulse 84; no cardiovascular. But for the next half hour,the bells > the turn-on. At three hours, almost baseline, and I eatmodestly. I have better things to do with my time."
There is the irrepressible fascination of this type of research. Couldone tinker with the molecule to emphasize one new property andde-emphasize another? Here is the theoretical conundrum stripped ofarcane chemical words and put into non-technical symbolism. Give asingle letter to a substitution group, increasing as the groupincreases in size. Here is the code:
A = hydrogen
B = methyl
C = ethyl
D = propyl
E = isopropyl
F = butyl
G = s-butyl
And let's arrange the 5-methoxylated tryptamines in order ofincreasing mass, and see if there is a pattern apparent as to thequantity or quality of action.
A A 5-MeO-T anti-radiation, not a psychedelic ?
A B 5-MeO-NMT unknown activity ?
B B 5-MeO-DMT, positive, psychedelic, out-of-body, 6-20 mg
B E 5-MeO-MIPT mixed, complex 4-6 mg
C C 5-MeO-DET negative, vertigo, erotic, 2-3 mg
C-- C 5-MeO-pyr-T very negative, amnesia 0.5-2 mg
D D 5-MeO-DPT neutral, balance, good and bad 6-10 mg
E E 5-MeO-DIPT positive, LSD-like psychedelic, 8-12 mg
F F 5-MeO-DBT known compound, unknown activity ?
G G 5-MeO-DSBT unknown compound -
So, I ask, how could C C be modified to eliminate the vertigocomponent, maintain the erotic component, perhaps even maintain thepsychedelic component, and certainly maintain the orally activeproperty. Clearly, tying them together in the form of a pyrrolidinering didn't do it. Only one of these listed 5-methoxy of knownactivity is asymmetric, the methyl isopropyl analogue. It is probablythrough this device of mixing and comparing, that our answer will befound. Some guide might come from the 5-hydrogen counterparts, more ofwhich have been explored in man. The variations with a constantisopropyl group have been organized in the recipe for EIPT. Here isthe rest of the story.
B C MET positive, psychedelic 80-100 mg
B D MPT unknown > 50 mg
B E MIPT mixed, complex 10-25 mg
B F MBT mixed 250-400 mg
B G MSBT unknown ?
C E EIPT mixed 24-40 mg
My hope is that getting leads from the second list (no substituent atthe indolic 5-position) could help guide the choice of asymmetricsubstituents for the first list (a methoxy group at the 5-position)that would lead to an expected increase in potency but to anunexpected change in quality of action.
Kierkegaard probably summed it up, best. "Life is not a problem to besolved, it is a mystery to be lived." That's chemistry, friends;that's life!
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