2,6-Lutidine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-vinyl-pyrazin-2-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 470 mg, 1.42 mmol) in methylene chloride (7 mL) was cooled to 0° C. and then was treated with a 2.0M solution of oxalyl chloride in methylene chloride (817 μL, 1.63 mmol) and N,N-dimethylformamide (1 mL). The reaction mixture was stirred at 0° C. for 30 min, concentrated in vacuo, and azeotroped with methylene chloride (3×2 mL). The resulting oil was then dissolved in tetrahydrofuran (10 mL) at 25° C. and then treated dropwise with a solution of 2-amino-5-vinylpyrazine (207 mg, 1.71 mmol) and 2,6-lutidine (198 μL, 1.71 mmol) in tetrahydrofuran (8 mL) via an addition funnel. The resulting cloudy solution was then stirred 25° C. overnight for 16 h. After this time, the reaction was diluted with water (10 mL) and then extracted with methylene chloride (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 65/35 to 20/80 hexanes/ethyl acetate) afforded the 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-vinyl-pyrazin-2-yl)-propionamide (472 mg, 77%) as a light yellow solid: (ES)+-HRMS m/e calcd for C21H24ClN3O3S (M+H)+ 434.1300, found 434.1301.

Provenance & Evidence