N,N'-Dicyclohexylurea → 2-(4-dimethylamino-4-phenylcyclohexylidene)-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 ml) were added in succession to a solution of 4-dimethylamino-4-phenylcyclohexylidene-acetic acid (891 mg, 3.0 mmole) in dry dimethylformamide (15 ml) under argon. 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 thereby 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 whole was kept for three days at 5° C. The crude product consisting of the amide precipitated out as a beige-coloured solid (994 mg). After chromatographic separation on silica gel (80 g) with EE/methanol (1:1), 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]ethanone was isolated as a colourless solid with an m.p. of 94°-97° C. in a yield of 46% (585 mg). The compound was obtained as a diastereoisomer mixture.

Provenance & Evidence