Pyridine → 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-pyrazin-2-yl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2(R)-(3,4-dichlorophenyl)-propionic acid (prepared as in Example 54A, 200 mg, 0.70 mmol) in methylene chloride (5 mL) was cooled to 0° C. and then treated with a 2M solution of oxalyl chloride in methylene chloride (0.52 mL, 1.0 mmol) and N,N-dimethylformamide (1 drop). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of 2-aminopyrazine (133 mg, 1.4 mmol) in tetrahydrofuran (10 mL) followed by pyridine (0.28 ml, 3.5 mmol). The resulting reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was then diluted with water (10 mL) and extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 70/30 hexanes/ethyl acetate) afforded 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-pyrazin-2-yl-propionamide (192 mg, 76%) as a colorless oil: [α]23589=−62.1° (c=0.095, chloroform); EI-HRMS m/e calcd for C18H19N3OCl2 (M+) 363.0905, found 363.0893.

Provenance & Evidence