Pyridine → 2-(3-chloro-4-methanesulfonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-pyran-4-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid (165 mg, 0.48 mmol) in methylene chloride (12 mL) and N,N-dimethylformamide (1 drop) cooled to 0° C. was treated dropwise with a 2.0M solution of oxalyl chloride in methylene chloride (0.27 mL, 0.55 mmol). The reaction was stirred at 0° C. for 30 min. At this time, the reaction was concentrated in vacuo to yield a light yellow oil. This oil was dissolved in tetrahydrofuran (5 mL) and then treated with a solution of 2-aminopyrazine (91 mg, 0.95 mmol) dissolved in tetrahydrofuran (10 mL) and pyridine (0.19 mL, 2.4 mmol). The reaction was then stirred at 25° C. for 16 h. At this time, the reaction was diluted with water (15 mL) and extracted with methylene chloride (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 25/75 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydro-pyran-4-yl)-propionamide (100 mg, 50%) as a white foam: (ES)+-HRMS m/e calcd for C19H22ClN3O4S (M+H)+ 424.1093, found 424.1095.

Provenance & Evidence