Tryptamine, N-isopropyl-N-methyl · Indole, 3-[2-(isopropylmethylamino)ethyl] · N-Isopropyl-N-methyltryptamine · 3-[2-(Isopropylmethylamino)ethyl]indole
#47 MIPT SYNTHESIS: (from tryptamine via ): A solution of 3.36 g tryptamine in 50 mL toluene was combined with another solution containing 5.52 g K2CO3 in 50 mL H2O and vigorously stirred at room temperature. To this there was added, dropwise, a solution of 3.0 mL benzyl chloroformate in 20 mL toluene. Stirring was continued for 15 h, then the reaction was treated with 200 mL EtOAc, the organic layer separated, and dried with anhydrous MgSO4. After filtration, the solvent was removed under vacuum, and the solid residue recrystallized from Et2O/hexane to give 5.25 g (85%) N-(benzyloxycarbonyl)tryptamine with a mp of 84–86 °C. Anal: C,H,N.
A suspension of 0.76 g LAH in 50 mL anhydrous THF was stirred under an inert atmosphere, and treated with the dropwise addition of a solution of 2.27 g N-(benzyloxycarbonyl)tryptamine in 30 anhydrous THF. The reaction mixture was held at reflux for 40 min, then cooled to 40 °C and the excess hydride destroyed with the addition of 50% aqueous THF. The solids were removed by filtration, washed with THF, the filtrate and washings combined, and the solvent removed under vacuum. The residue was impure N-methyltryptamine () as could be used without purification in the following alkylation. The isolation, purification and characterization of this intermediate amine is described in the NMT recipe, and of course the pure NMT can be used in the following reductive alkylation.
The crude N-methyltryptamine obtained above (which can be substituted with 1.20 g of pure ) was dissolved in 50 mL ethanol EtOH, treated with 1.0 mL acetone, then with 0.5 g 10% Pd/C, and the reaction mixture shaken under a hydrogen atmosphere at 50 psi for 15 h. The catalyst was removed by filtration through a bed of Celite, the filtrate was stripped of solvent under vacuum, and the solid residue recrystallized from Et2O/hexane to give 0.93 g N-methyl-N-isopropyltryptamine (MIPT) which had a mp 82–83 °C. Fom the benzyloxycarbonyltryptamine, yield was 56%. From NMT the yield was 62% of theory. Anal: C14H20N2. C,H,N. MS (in m/z): C5H12N+ 86 (100%); indolemethylene+ 130 (10%); parent ion 216 (2%). Efforts to isopropylate NMT with an excess of isopropyl iodide in isopropanol IPA gave a 51% yield of a distilled product that did not crystallize.
(from N-isopropyltryptamine, ): A solution of 0.47 g of N-isopropyltryptamine hydrochloride in 50 mL H2O was made basic with 5% aqueous NaOH, and extracted with 3×40 mL CH2Cl2. The pooled extracts were stripped of solvent and the solid residue was dissolved in 25 mL IPA and treated with 0.35 g CH3I. After 3 h at reflux, an additional 10 mL IPA and 0.14 g CH3I were added and the reflux continued for 6 h. After removal of the solvent under vacuum, the residue was partitioned between dilute base and CH2Cl2. Removal of the solvent under vacuum yielded 0.29 g of an oil that was shown chromatographically to be a mixture of NIPT and MIPT in a 3:2 ratio. This was treated with 0.35 g CH3I in 25 mL IPA and allowed to stand at room temperature for several days. A small quantity of crystals separated (N,N-dimethyl-N-isopropyltryptammonium iodide) which were removed by filtration. The filtrate was stripped of solvent under vacuum, and the residue again partitioned, as above, between aqueous NaOH and CH2Cl2. After removing the organic solvent, the residue (0.23 g NIPT to MIPT ratio 2:3) was treated with 0.5 g acetic anhydride, heated on the steam bath for 1 h, diluted with 5% aqueous NaOH and stirred for 2 h. This was extracted with 3×40 mL CH2Cl2, the extracts were pooled, and then extracted with 3×40 mL N H2SO4. The pooled acid extracts were made basic with NaOH, reextracted with CH2Cl2 which, on pooling and the removal of the solvent under vacuum, gave 0.12 g of a colorless oil. Distillation at 0.1 mm/Hg (140–150 °C) gave 0.06 g (a 15% yield) of N-Isopropyl-N-methyltryptamine as a colorless oil that spontaneously crystallized.
DOSAGE: 10–25 mg, orally
DURATION: 3–4 hrs h
QUALITATIVE COMMENTS: (with 5 mg, orally) “Maybe a hint towards the end of an hour. Nothing further. Slept soundly.”
(with 10 mg, orally) “There is no question but what this is active. I felt it just a half hour after taking it, and was somewhat disappointed to see it disappear over the next couple of hours. A very good feeling, quite randy.”
(with 10 mg, orally) “Definitely active, mild excitement, dry mouth, some muscle tension in the back of the neck. At 75 minutes, definitely rolling, but still no visual effects. Finally subsiding. Not unpleasant, although a feeling of restlessness persists. Tailing insomnia for 6–8 hours.”
(with 20 mg, orally) “My handwriting is shot. There are almost no visuals, so why am I at a plus two? I feel very alert. Tried to sleep and ended up talking for quite a while instead The overall experience can best be described as ‘mild’.”
(with 25 mg, orally) “Quite an active dose. Same initial effects as with 10 milligrams, but considerably more excitement, central stimulation. At an hour, the effects seem to have plateaued. Enhancement of visual field, i.e., brightened colors, clearly defined objects. Definite auditory effects, and I can pick out each sound with clear definition. Very ‘heady,’ but still remarkably free of visual distortion. Slight mydriasis. As it subsides, there is some muscle tension in the jaws, but much milder than with or even .”
(with 20 mg, by insufflation) “Immediate onset (less than a minute) and to ++. A little dizziness. My first thought is, ‘This is definitely psychedelic.’ Everything looked brighter, and vision was tinted orange. Everything appeared as if under an orange overlay. No other visual changes to speak of. Skin, hearing, sensitive. All-in-all, however, sensory changes were minor. The effects on thought were more typically psychedelic. The spin-offs, tangents, and implications of different threads of thought became apparent, and I could watch them unfold with my mind’s eye. These effects gradually tapered off over the next three and a half hours or so. During this time, interaction with my companions was facile, and we had a good conversation. This compound seems to emphasize ‘psychedelic’ effects over ‘hallucinogenic’ effects.”
EXTENSIONS AND COMMENTARY: This is the simplest tryptamine with the somewhat magical pair of nitrogen substituents, a methyl group and an isopropyl group. Why should this combination allow a molecule to be orally active, even though the conventional thinking is that if there is a methyl group there, the amine oxidases will destroy it? My sense is that it is the N-small-group that does the job in the brain, and it is the N-big-group that keeps the inactivating oxidase enzymes away from the nitrogen atom. This is consistent with the N,N-dimethyl compound () not being orally active. Lying midway between DMT and is the ethyl compound, N-ethyl-N-methyltryptamine, or . It can be made by adding ethyl acetate to a reaction mixture where the formamide of tryptamine (see under ) has been reduced to NMT but there is still a goodly excess of hydride still remaining. The free base, as an oil, shows oral activity in the eighty to one hundred milligram range, so going from a methyl to an ethyl does indeed protect the compound from total enzymatic annihilation when taken orally.
The isomer of MIPT with a considerably less bunched up propyl group, N-methyl-N-propyltryptamine or . This was made via the amide from indoleglyoxyl chloride and methylpropylamine, and reduction with LAH. MS (in m/z): C5H12N+ 86 (100%); indolemethylene+ 130 (8%); parent ion 216 (1%). Several human trials, up to twenty milligrams orally, showed no effects of any kind, so the activity, if there is any, is definitely less than that of MIPT. So the lumpiness of the isopropyl may be playing some role. There is no other way that is obvious of challenging this without adding more carbon atoms, and that would introduce another variable. This same decoration scheme has been used successfully in several other of the tryptamines in this story.
A couple points of passing interest. As to stability: many of the free-base tryptamines are sensitive to air oxidation, some of them extremely so. This particular base, standing for a goodly number of years with no particular protection from air, has remained almost colorless, with no apparent signs of decomposition. And as to subjective effects: there is almost a total lack of visual phenomena. There were no wave-forms, color distortion or object shape changes, and no eyes-closed imagery, unlike most N,N-disubstituted tryptamines.
13 May 2016 · Creative Commons BY-NC-SA ·

About TiHKAL · info

This version of Book II of TiHKAL is based on the Erowid online version created by Bo Lawler with the help of Erowid, from content generously provided in electronic format by the Authors.
The Erowid online version does not always align precisely with the printed version. Text appears to have been inserted, deleted, or changed at various points. Where the two are seen to diverge both the Erowid and print versions are given. Sharp-eyed readers are encouraged to report novel discrepancies.
As with PiHKAL, I’ve again attempted to reproduce the typographic style of the printed edition. I’ve again made minor changes to some chemical names in line with current nomenclature practice. Typically the change is little more than expanding a prefix or setting it in italics. The history page has further details.

Cautionary note

“At the present time, restrictive laws are in force in the United States and it is very difficult for researchers to abide by the regulations which govern efforts to obtain legal approval to do work with these compounds in human beings.
“No one who is lacking legal authorization should attempt the synthesis of any of the compounds described in these files, with the intent to give them to man. To do so is to risk legal action which might lead to the tragic ruination of a life. It should also be noted that any person anywhere who experiments on himself, or on another human being, with any of the drugs described herein, without being familiar with that drug’s action and aware of the physical and/or mental disturbance or harm it might cause, is acting irresponsibly and immorally, whether or not he is doing so within the bounds of the law.”
Alexander T. Shulgin

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The copyright for Book I of TiHKAL has been reserved in all forms and it may not be distributed. Book II of TiHKAL may be distributed for non-commercial reproduction provided that the introductory information, copyright notice, cautionary notice and ordering information remain attached.

Ordering information

TiHKAL is the extraordinary record of the authors’ years exploring the chemistry and transformational power of tryptamines. This book belongs in the library of anyone seeking a rational, enlightened and candid perspective on psychedelic drugs.
Though Sasha and Ann have put Book II of TiHKAL in the public domain, available to anyone, I strongly encourage you to buy a copy. We owe them — and there’s still nothing quite like holding a real book in your hands.
TiHKAL (ISBN 0-9630096-9-9) is available for US$24.50 (plus $10 domestic first-class shipping) from Transform Press.
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