Another tryptamine methylation / dequaternization

[Rhodium]

6-(Methylthio)-N,N-dimethyltryptamine Methiodide

Crude 6-Methylthiotryptamine (4.95 g, 0.025 mol) was dissolved in 300 mL of MeOH containing 10.6 g (0.08 mol) of CH3I and 6.3g (0.08 mol) of NaHCO3. This mixture was refluxed for 72 h, and 2 g of CH3I was added at 24 and 48 h, respectively. Removal of the solvent in vacuo gave a colorless solid, which was recrystallized from boiling EtOH (Norite) to give 3.3 g (36%) of 6-(Methylthio)-N,N-dimethyltryptamine Methiodide as colorless needles: mp 215-217°C;

6-(Methylthio)-N,N-dimethyltryptamine

6-(Methylthio)-N,N-dimethyltryptamine Methiodide (2.2 g, 6 mmol) was refluxed in 50 mL of DMF containing 1.3 g (11.5 mmol) of 1,4-diazabicyclo[2.2.2]octane (DBO) for 3 h. The reaction mixture was diluted with 300 mL of H2O and then extracted with 600 mL of a 1:2 mixture of EtOAc/benzene, and the organic layer was back-extracted with 10% HCl. Basification of the aqueous layer with 5 N NaOH liberated the crude amine, which was extracted with EtOAc. After drying (MgSO4), the solvent was evaporated to yield a dark-yellow oil, which was subjected to Kugelrohr distillation (140°C, 0.01 mm). Recrystallization of the viscous distillate from benzene/petroleum ether yielded 0.543 g (33%) of pure 6-(Methylthio)-N,N-dimethyltryptamine, mp 62-63°C

Reference: J. Med. Chem. 25, 908-913 (1982)

[obia]

this demethylation with dabco also works in dmso. though the reaction has no advantages over ethanolamine.

[Rhodium]

5-(1,2,4-triazolylmethyl)-N,N-dimethyltryptamine

A solution of formaldehyde (0.30 g of a 37%, w/v, solution, 3.7 mmol) in MeOH (10 mL) was added to a stirred mixture of 5-(1,2,4-triazolylmethyl)- tryptamine (0.36 g, 1.5 mmol), NaCNBH3 (0.225 g, 3.6 mmol), and glacial acetic acid (0.45 g, 7.5 mmol), in MeOH (10 mL), at 0°C. The solution was warmed to 25°C and stirred for 2 h before adding saturated K2CO3 solution (5 mL). The MeOH was removed under vacuum, H2O (10 mL) was added, and the mixture was extracted 3x with ethyl acetate. The combined extracts were washed once with brine and dried and the solvent evaporated. The crude product was chromatographed on silica gel eluting with CH2Cl2/EtOH/NH3 (40:8:1) to give 5-(1,2,4-triazolylmethyl)- N,N-dimethyltryptamine (0.21 g, 52%).

Reference: J. Med. Chem. 38, 1799-1810 (1995)