TiHKAL #41 5,6-MEO-MIPT

SYNTHESIS : To a suspension of 0.88 g 5,6-dimethoxyindole in 50 mL Et2O, stirred and cooled with an external ice bath, there was added, dropwise, a solution of 0.87 g oxalyl chloride in 5 mL Et2O over the course of 20 min. The mixture was stirred for an additional 20 min, and then the glyoxyl chloride was removed by filtration, washed with Et2O, and dried under vacuum. A suspension of this red solid in 50 mL of ice-cold dry THF, under nitrogen, was treated with the dropwise addition of a 30% solution of methyl isopropyl amine in Et2O, until the pH exceeded 9. The solvents were removed under vacuum, and the residue partitioned between CHCl3 and H2O. The organic phase, after decolorization with charcoal, was stripped of solvent under vacuum and the solid residue recrystallized from EtOAc / hexane. There was thus obtained 0.61 g 5,6-dimethoxy-N-isopropyl-N-methylindoleglyoxylamide, with mp 204-206 °C (yield 40%).

A well-stirred suspension of 0.55 g LAH in 25 mL anhydrous THF was treated, dropwise, with a solution of 0.53 g 5,6-dimethoxy-N-isopropyl-N-methylindoleglyoxlamide in 75 mL anhydrous THF. The reaction mixture was brought to reflux temperature, held there for 30 min, and cooled to about 40 °C. There was added 0.55 mL H2O followed by 1.65 mL 10% aqueous NaOH and an additional 0.55 mL H2O. The solids were removed by filtration and the filter cake washed with THF. The combined filtrate and washings were stripped of solvent under vacuum. The oily residue was crystallized from hexane to give 0.34 g (yield 71%) 5,6-dimethoxy-N-isopropyl-N-methyltryptamine, mp 71-73 °C. MS (in m/z): C5H12N+ 86 (100%); indolemethylene+ 190 (4%); parent ion 276 (9%).

(with 75 mg, orally) "There was a vague awareness of something at about the one-hour point. Not enough to even be called a threshold effect."

EXTENSIONS AND COMMENTARY : This compound, having no detectable activity even at the milligram / kilo level, pretty much condemns the 5,6-dimethoxy indole pattern. Quite a few closely related derivatives have been made; there is the N,N-dimethyl (5,6-MeO-DMT), the N,N-diethyl (5,6-MeO-DET), the N,N-dibutyl (5,6-MeO-DBT) and the three famous heterocyclic ring compounds, the pyrrolidyl (5,6-MeO-pyr-T), the piperidyl (5,6-MeO-pip-T) and the morpholyl (5,6-MeO-mor-T) compounds. They were all synthesized and characterized in the 1960's, but I have no record of any having been tried in man.

One desoxy analogue warrants mention. This is known as 5-methoxy-6-methyl-DMT (5,6-MeOM-DMT) or as 5-methoxy-6,N,N-trimethyltryptamine (5-MeO-6,N,N-TMT), where the 6-methoxy group is, in effect, replaced with a 6-methyl group. Having a DMT skeleton, it was assayed parenterally, and even at 15 milligrams (smoking) there was nothing noted. This is a level that would have been dramatic had there been no substitution at that 6-position. Some of the historical background of an oxygen at this position is discussed in the 6-HO-DMT recipe.