2,6-Lutidine → 2(R)-(3-chloro-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-methoxy-phenyl)-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, 300 mg, 0.91 mmol) in methylene chloride (15 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (522 μL, 1.04 mmol) and N,N-dimethylformamide (1 drop). The reaction mixture was stirred at 0° C. for 30 min, concentrated in vacuo, and azeotroped with methylene chloride (2 mL) two times. The resulting oil was dissolved in tetrahydrofuran (5 mL) at 25° C. and then treated dropwise with a solution of 5-(3-methoxy-phenyl)-pyrazin-2-ylamine (201 mg, 1.00 mmol) and 2,6-lutidine (126 μL, 1.09 mmol) in tetrahydrofuran (6 mL) via an addition funnel. The resulting cloudy solution was then stirred overnight for 16 h at 25° C. 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, 3/1 to 3/2 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-methoxy-phenyl)-pyrazin-2-yl]-propionamide (388 mg, 83%) as a light yellow foam: (ES)+-HRMS m/e calcd for C26H28ClN3O4S (M+H)+ 514.1562, found 514.1567.

Provenance & Evidence