Water → HCID 10254648, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-{5-[2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazin-2-yl}-malonic acid diethyl ester (189 mg, 0.33 mmol) in tetrahydrofuran (5.0 mL) cooled to 0° C. was treated with a 1.0M solution of diisobutylaluminum hydride in hexanes (1.84 mL, 1.84 mmol). The reaction mixture was stirred at 0° C. for 1.25 h and then at 25° C. for 2 h. At this time, the reaction was re-cooled to 0° C. and was treated with an additional amount of a 1.0M solution of diisobutylaluminum hydride in hexanes (0.92 mL, 0.92 mmol). The reaction was stirred at 0° C. for 15 min and then at 25° C. for 1 h. At this time, the reaction mixture was poured onto a mixture of ice, water, and ethyl acetate. The aqueous layer was extracted with ethyl acetate and diethyl ether. The combined organic layers were washed with a 1N aqueous citric acid solution, a cold saturated aqueous sodium bicarbonate solution, a saturated aqueous sodium chloride solution, dried over magnesium sulfate and sodium sulfate, treated with charcoal, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 9/1 ethyl acetate/acetonitrile) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2-hydroxy-1-hydroxymethyl-ethyl)-pyrazin-2-yl]-propionamide (17.9 mg, 11%) as a pale yellow foam: mp 110–120° C.; (ES)+-HRMS m/e calcd for C22H28N3O5 (M+H)+ 482.1511, found 482.1512.

Provenance & Evidence