Potassium Cyanide → 2-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyano-pyrazin-2-yl)-3-(tetrahydro-pyran-4-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionamide (prepared as in Example 21, 325 mg, 0.65 mmol) in N,N-dimethylformamide (5 mL) at 25° C. was treated with potassium cyanide (105 mg, 1.62 mmol), copper(I) iodide (307 mg, 1.62 mmol), tetrakis(triphenylphosphine)palladium(0) (22 mg, 0.02 mmol), and 18-crown-6 (25 mg, 0.09 mmol). This reaction mixture was then heated to 150° C. under argon for 5 h. At this time, the reaction was cooled to 25° C., concentrated to half the volume, and then chloroform (40 mL) was added until all the salts precipitated out of solution. The salts were removed by filtration through a pad of celite and washed with chloroform. The filtrate was then concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 30/70 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyano-pyrazin-2-yl)-3-(tetrahydro-pyran-4-yl)-propionamide (219 mg, 76%) as a white foam: (ES)+-HRMS m/e calcd for C20H21ClN4O4S (M+H)+ 449.1045. found 449.1046.

Provenance & Evidence