Pyridine → Piragliatin;RO 4389620

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-propionic acid (594.8 mg, 1.725 mmol) in methylene chloride (8.6 mL) and N,N-dimethylformamide (2 drops) cooled to 0° C. was treated with oxalyl chloride (226 μL, 2.587 mmol). The reaction mixture was stirred at 0° C. for 15 min and then stirred at 25° C. for 2 h. The reaction mixture was concentrated in vacuo to afford a red oil. This red oil was dissolved in tetrahydrofuran (4.03 mL), cooled to 0° C., and then slowly treated with a solution of 2-aminopyrazine (246.1 mg, 2.587 mmol) and pyridine (209 μL, 2.587 mmol) in tetrahydrofuran (4.3 mL). The resulting reaction mixture was stirred at 0° C. for 15 min and then stirred at 25° C. for 2 h. The reaction mixture was quenched with a 1N aqueous citric acid solution (20 mL) and then extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (2×100 mL) and a saturated aqueous sodium chloride solution (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80% ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide (207.3 mg, 28%) as a pale yellow foam: mp 93-96° C. (foam to gel); (ES)+-HRMS m/e calcd for C19H20ClN3O4S (M+H)+422.0936. found 422.0938.

Provenance & Evidence