Hydrochloric Acid → 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyrazin-2-yl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 75, 200 mg, 0.622 mmol) in methylene chloride (5 mL) was treated with N,N-dimethylformamide (2 drops) and then cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (0.081 mL, 0.933 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 1 h. The reaction mixture was then concentrated in vacuo. The resulting yellow gel was diluted with methylene chloride (2 mL) and then slowly added to a mixture of 2-aminopyrazine (89 mg, 0.933 mmol) and triethylamine (0.173 mL, 1.24 mmol) in N,N-dimethylformamide (3 mL). The resulting reaction mixture was stirred at 25° C. for 24 h. The reaction mixture was then diluted with water (30 mL), a 1N aqueous hydrochloric acid solution (5 mL), and ethyl acetate (30 mL). The layers were separated, and the organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 19/1 methylene chloride/methanol) afforded 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyrazin-2-yl-propionamide as an impure orange foam. Re-purification by flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) afforded 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyrazin-2-yl-propionamide (8 mg, 3%) as a yellow foam: mp 88-93° C. (foam to gel); EI-HRMS m/e calcd for C20H22N4O3S (M+) 398.1413, found 398.1413.

Provenance & Evidence