Pyridine → 5-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 196.4 mg, 0.59 mmol) in methylene chloride (3 mL) was cooled to 0° C. The reaction mixture was then treated with N,N-dimethylformamide (1 drop) and oxalyl chloride (109 μL, 1.25 mmol). The reaction mixture was stirred at 0° C. for 15 min and then at 25° C. for 2 h. The solution was then concentrated in vacuo. The yellow slurry was dissolved in methylene chloride (1 mL) and cooled to 0° C. To this solution was added a suspension of 5-amino-pyrazine-2-carboxylic acid methyl ester (100.0 mg, 0.65 mmol) and pyridine (53 μL, 0.6529 mmol) in warm methylene chloride (2 mL). The reaction mixture was stirred at 0° C. for 30 min and then at 25° C. for 3 h. The reaction mixture was then concentrated in vacuo. The reaction material was diluted with ethyl acetate (50 mL) and washed with a saturated aqueous sodium bicarbonate solution (100 mL), a saturated aqueous sodium chloride solution (100 mL), a 1N aqueous hydrochloric acid solution (100 mL), and a saturated aqueous sodium chloride solution (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 ethyl acetate/hexanes) afforded 5-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid methyl ester (225.9 mg, 82%) as a white foam: mp 94–97° C. (foam to gel); (ES)+-HRMS m/e calcd for C21H24ClN3O5S (M+H)+466.1198, found 466.1204.

Provenance & Evidence