Pyridine → N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-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 (prepared as in Example 20, 470 mg, 1.36 mmol) in methylene chloride (25 mL) and N,N-dimethylformamide (1 drop) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.78 mL, 1.56 mmol) and then 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 (10 mL) and then treated with a solution of 2-amino-5-bromopyrazine (472 mg, 2.71 mmol, prepared according to Tetrahedron 1988, 44, 2977-2983) in tetrahydrofliran (20 mL) and pyridine (0.55 mL, 6.78 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 organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 40/60 hexanes/ethyl acetate) afforded N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionamide (477 mg, 70%) as a yellow foam: (ES)+-HRMS m/e calcd for C19H21ClBrN3O4S (M+H)+ 502.0198. found 502.0205.

Provenance & Evidence