N,N'-Dicyclohexylurea → 2-(4-dimethylamino-4-phenylcyclohexyl)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone

Participants

Reaction Steps

1-hydroxybenzotriazole (810 mg, 6.0 mmole), 3-pyrrolidine-3-yl-1H-indole (558 mg, 3.0 mmole) and N-methylmorpholine (0.666 ml, 6.0 mmole) were added in succession under argon to a solution of (4-dimethylamino-4-phenylcyclohexyl)-acetic acid (897 mg, 3.0 mmole) in dry dimethylformamide (15 ml). The solution was cooled in an ice bath and dicyclohexylcarbodiimide (1.2 g, 6.0 mmole) was added. The reaction mixture was stirred for 4 days at RT, the dicyclohexylurea precipitating out little by little. The reaction mixture was worked up by separating the precipitated urea and adding the filtrate to a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml). Further urea thereupon precipitated out, which was separated. The aqueous phase was diluted with water (300 ml), 5M sodium hydroxide (7 ml, 35 mmole) was added, and the reaction mixture was kept for 3 days at 5° C. The crude product of 2-(4-dimethylamino-4-phenylcyclo-hexyl)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone precipitated out as a beige-coloured solid (1.11 g). After chromatographic separation on silica gel (80 g) with methanol 2-(4-dimethylamino-4-phenylcyclohexyl)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone was isolated in a yield of 40% (521 mg) as a colourless solid with an m.p. of 98°-100° C.

Provenance & Evidence