Pyridine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-thiophen-2-yl-pyrazin-2-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (230.0 mg, 0.877 mmol) in methylene chloride (15 mL) cooled to 0° C. was treated with N-bromosuccinimide (160.0 mg, 0.899 mmol). The reaction mixture was stirred at 0° C. for 5 min and then treated with 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 232.0 mg, 0.701 mmol). The reaction mixture was allowed to warm to 25° C. over 15 min. The reaction mixture was then treated with 5-thiophen-2-yl-pyrazin-2-ylamine (260.0 mg, 1.467 mmol) followed by pyridine (0.24 mL, 2.967 mmol). The resulting reaction mixture was stirred at 25° C. for 1 h. The reaction mixture was then diluted with methylene chloride and washed with a dilute aqueous hydrochloric acid solution. The aqueous layer was back-extracted with methylene chloride. The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution and water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 3/1 to 3/2 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-thiophen-2-yl-pyrazin-2-yl)-propionamide (202.3 mg, 58.9%) as a yellow foam: mp 97–99° C. (foam to gel); (ES)+-HRMS m/e calcd for C23H24ClN3O3S2 (M+H)+ 490.1021, found 490.1026.

Provenance & Evidence