#28. 4,5-MDO-DIPT

[3D .mol Image]

SYNTHESIS : A solution of 4.8 g 4,5-methylenedioxyindole (see under 4,5-MDO-DMT for its preparation) in 60 mL anhydrous Et2O was stirred and cooled with an external ice bath. There was added, dropwise, a solution of 5.0 g oxalyl chloride in Et2O so that the temperature did not exceed 5 °C. The intermediate acid chloride separated as a red solid, and was removed by filtration and washed with Et2O. It was then suspended in 60 mL cold anhydrous Et2O, treated with 14 mL diisopropylamine and the mixture stirred for 30 min. The solvent was decanted from the crude solids that formed, and they were suspended in 50 mL H2O. The product was removed by filtration and vacuum dried to provide 5.3 g (56%) 4,5-methylenedioxy-N,N-diisopropylindole-3-glyoxylamides a white solid, with a mp 260 °C (dec).

To a stirred and cooled solution of 3.8 g LAH in 100 mL anhydrous THF there was added, over the course of 1 h, a solution of 4.70 g 4,5-methylenedioxy-N,N-diisopropylindole-3-glyoxylamide in 500 mL anhydrous THF. After 1 h reflux, the cooled reaction mixture was treated with 3.8 mL H2O, followed by 3.8 mL aqueous 5% NaOH and then by an additional 10.4 mL H2O. The solids were removed by filtration and washed with THF. The combined filtrate and washings were dried (MgSO4) and the solvent removed under vacuum. The residual oil was distilled at the KugelRohr (0.5 mm/Hg at 100 °C) to give a distillate that solidified. This was crystallized from benzene/hexane to provide 1.34 g (31%) of 4,5-methylenedioxy-N,N-diisopropyltryptamine (4,5-MDO-DIPT) with mp 109-113 °C. Anal: C, H. N.

DOSAGE : > 25 mgs

DURATION : unknown

QUALITATIVE COMMENTS : (25 mg, orally) Nothing much happened for about 3 hours, and then I suddenly shot up. I was at the plateau for a fair time, the recovery was difficult to define chronologically. This was in daylight; I was reminded very much of LSD.

EXTENSIONS AND COMMENTARY : This is the second of the two tryptamines known with the most appealing methylenedioxy ring bridge located at the two most sensitive ring positions of the indole nucleus. It, too, is an unknown entity. There is a single observation of an oral trial, and it suggests something of interest at 25 milligrams. Higher dosages might prove most interesting. There is no question that the methyl isopropyl homologue of this compound, 4,5-MDO-MIPT would be a rewarding compound to assay. As of the present moment, it has not yet been synthesized. It should be a relatively easy one to make.

There is an interesting parallel to be seen here. This methylenedioxy hetero-ring is snuggled as closely as possible to the ethylamine chain of the indole (the 4-position occupied by the nearer oxygen atom, and the indole chain at the 3-position). There is the same intimacy possible in the phenethylamine world. This would be realized by moving the methylenedioxy ring of MDA (3,4-methylenedioxyamphetamine) to the 2,3-location. Here, again, the nearer oxygen would be as close as possible to the ethylamine chain at the 1-position. This compound, 2,3-methylenedioxyamphetamine, has been made by several research groups, and has been looked at in man. At 50 milligrams, orally, it produced some pretty strong stimulatory effects, with no sleep found to be possible during the following 24 hours. But, on the other hand, it seemed to be devoid of MDA-like effects. This positional isomer was mentioned in PIHKAL.

There is no way to meaningfully extrapolate from this phenethylamine analogue 2,3-MDA to 4,5-MDO-DIPT, but it does present a very close structural relationship that could be used to justify a clinical study of this unusual tryptamine.