Pyridine → HCID 86593786, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 5-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid (401.6 mg, 0.889 mmol) in methylene chloride (4.4 mL) was cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (310 μL, 3.554 mmol) and N,N-dimethylformamide (2 drops). The reaction mixture was stirred at 0° C. for 45 min and then slowly warmed to 25° C. over 1 h 45 min. The solution was then concentrated in vacuo. The residue was dissolved in methylene chloride (3.4 mL) and cooled to 0° C. The resulting solution was then treated with a mixture of O-(tert-butoxyl)hydroxylamine hydrochloride (133.3 mg, 1.061 mmol) and pyridine (180 μL, 2.226 mmol) in tetrahydrofuran (4.4 mL), followed by a methylene chloride rinse (1 mL). The reaction mixture was stirred at 0° C. for 45 min and then stirred at 25° C. for 2 h 15 min. The reaction was then quenched with water (5 mL) and stirred at 25° C. for 30–45 min. The reaction was partitioned between ethyl acetate (300 mL) and a 1N aqueous citric acid solution (250 mL), and the layers were seperated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution (250 mL), water (250 mL), and a saturated aqueous sodium chloride solution (250 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 2/3 to 1/1 ethyl acetate/hexanes) afforded 5-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid tert-butoxy-amide (338.8 mg, 73%) as an off-white foam: mp 128–131° C. (foam to gel); (ES)+-HRMS m/e calcd for C24H31ClN4O5S (M+H)+ 523.1777, found 523.1782.

Provenance & Evidence