Potassium Cyanide → 2(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-cyano-pyrazin-2-yl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-bromo-pyrazin-2-yl-propionamide (6.11 g, 13.5 mmol), potassium cyanide (2.27 g, 33.8 mmol), copper(I) iodide (6.43 g, 33.8 mmol), tetrakis(triphenylphosphine)palladium(0) (320 mg, 0.27 mmol), and 18-crown-6 (365 mg, 1.37 mmol) in anhydrous N,N-dimethylformamide (30 mL) was heated at 150° C. under argon. After 4 h, the mixture was allowed to cool to 25° C. The mixture was concentrated to about one-half volume and then chloroform (700 mL) was added to precipitate the copper salts. The mixture was filtered through a pad of celite, and the salts were washed with warm chloroform (2×100 mL). The filtrate was then concentrated in vacuo. Biotage chromatography (FLASH 75S, Silica, 0% to 35% gradient ethyl acetate/hexanes) afforded 2(R)-(4-methanesulfonyl-phenyl)-3-cyclopentyl-5-cyano-pyrazin-2-yl-propionamide (4.49 g, 83%) as a light yellow solid: mp 229–231° C.; (ES)+-HRMS m/e calcd for C20H23N4O3S2 (M+H)+ 399.1486, found 399.1488.

Provenance & Evidence