Water → 1-[(R)-1-benzyl-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indol-5-yl]-1-cyano-N-diphenylmethyl-N-methylmethanesulfonamide

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Reaction Steps

To a stirred solution of 1-cyano-N-diphenylmethyl-N-methylmethanesulfonamide (from step (c), 18.79 g, 62.6 mmol) in a mixture of toluene (60 ml) and ethylene glycol dimethylether (20 ml) at 0-5° C. under a nitrogen atmosphere was added sodium hydride (60% dispersion in mineral oil) (4.6 g, 115 mmol) portionwise, maintaining the temperature below 5° C. Upon completion of the addition, the dark brown solution was warmed to ambient temperature over a 30 min period, before tetrakis(triphenylphosphine) palladium(0) (3.61 g, 3.1 mmol) was added in one portion. A solution of (R)-1-benzyl-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indole (from Example 1(d), 19.74 g, 52 mmol) in toluene (20 ml) was then added dropwise to the brown slurry and the mixture was warmed to reflux. Reflux was maintained for 2 hr after which time the dark brown solution was cooled to ambient temperature. The reaction mixture was then poured into water (250ml) and extracted with ethyl acetate (3×100 ml). The organic extracts were combined and evaporated in vacuo to yield a brown oil. This was re-dissolved in absolute ethanol (80 ml) and stirred for 18 hr over which time precipitation occurred. The solid seas filtered and dried in vacuo at 50° C. overnight to yield the subtitle compound (22 g, 70%) as a cream solid. m.p. 152-155° C.

Provenance & Evidence