反应详情

温度

25 °C

A solution of N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (616.0 mg, 1.266 mmol), potassium cyanide (210.0 mg, 3.225 mmol), tetrakis(triphenylphosphine)palladium(0) (30.0 mg, 0.026 mmol), copper(I) iodide (605.0 mg, 3.177 mmol), and 18-crown-6 (33.0 mg, 0.125 mmol) in anhydrous N,N-dimethylformamide (6 mL) was heated at 150° C. under nitrogen. After 2.75 h, the mixture was allowed to cool to 25° C. The mixture was then concentrated to remove solvent. The residue was diluted with methylene chloride and ethyl acetate and then filtered through a pad of celite. The celite pad was then washed well with ethyl acetate and methylene chloride. The filtrate was then concentrated in vacuo and absorbed onto silica gel (Merck Silica gel 60, 230–400 mesh). Biotage chromatography (FLASH 40L, Silica, 1/3 to 1/1 ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyano-pyrazin-2-yl)-3-cyclopentyl-propionamide (402.3 mg, 73.4%) as an off-white foam: (ES)+-HRMS m/e calcd for C20H21ClN4O3S (M+H)+ 433.1096, found 433.1101.

1. concentrationThe mixture was then concentrated
2. customto remove solvent
3. additionThe residue was diluted with methylene chloride and ethyl acetate
4. filtrationfiltered through a pad of celite
5. washThe celite pad was then washed well with ethyl acetate and methylene chloride
6. concentrationThe filtrate was then concentrated in vacuo
7. customabsorbed onto silica gel (Merck Silica gel 60, 230–400 mesh)