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

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (149.0 mg, 0.568 mmol) in methylene chloride (8 mL) cooled to 0° C. was treated with N-bromosuccinimide (103.0 mg, 0.579 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, 150.0 mg, 0.453 mmol). The reaction mixture was allowed to warm to 25° C. over 15 min. The reaction mixture was then treated with 5-thiophen-3-yl-pyrazin-2-ylamine (168.0 mg, 0.948 mmol) followed by pyridine (0.16 mL, 1.978 mmol). The resulting reaction mixture was stirred at 25° C. for 1.5 h. The reaction mixture was then diluted with methylene chloride and washed with a dilute aqueous hydrochloric acid solution. The aqueous layer was extracted with methylene chloride. The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 3/1 to 2/1 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-thiophen-3-yl-pyrazin-2-yl)-propionamide (105.6 mg, 47.5%) as a pale yellow foam: mp 96–102° C. (foam to gel); (ES)+-HRMS m/e calcd for C23H24ClN3O3S2 (M+H)+ 490.1021, found 490.1023.

Provenance & Evidence