Pyridine → HCID 67482855, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 1.00 g, 3.02 mmol) in methylene chloride (15 mL) was cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (1.10 mL, 12.61 mmol) and N,N-dimethylformamide (2 drops). The reaction mixture was stirred at 0° C. for 30 min and then slowly warmed to 25° C. over 45 min. The solution was then concentrated in vacuo. The yellow slurry was dissolved in methylene chloride (15 mL) and then cooled to 0° C. To this solution was added a solution of 5-amino-pyrazine-2-carboxylic acid tert-butyl ester (0.71 g, 3.64 mmol) and pyridine (295 μL, 3.65 mmol) in tetrahydrofuran (15 mL). The reaction mixture was stirred at 0° C. and was slowly warmed to 25° C. overnight. The reaction was then quenched with a 1N aqueous citric acid solution (10 mL), stirred at 25° C. for 3 min, and then concentrated in vacuo. The reaction material was partitioned between ethyl acetate (400 mL) and a 1N aqueous citric acid solution (200 mL), and the layers were seperated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution (200 mL), water (200 mL), and a saturated aqueous sodium chloride solution (200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo onto silica gel (Merck Silica gel 60, 230–400 mesh). Biotage chromatography (FLASH 40L, Silica, 1/2 ethyl acetate/hexanes) afforded 5-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid tert-butyl ester (0.80 g, 52%) as a white foam: mp 107–111° C. (foam to gel); (ES)+-HRMS m/e calcd for C24H30ClN3O5S (M+H)+ 508.1668, found 508.1666.

Provenance & Evidence