Pyridine → 2-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyanomethyl-pyrazin-2-yl)-3-cyclopentyl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 33, 663.1 mg, 2.004 mmol) in methylene chloride (10 mL) was treated with N,N-dimethylformamide (2 drops) and then cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (357 μL, 4.009 mmol). The reaction mixture was stirred at 0° C. and then warmed to 25° C. where it was stirred for 1.5 h. At this time, the reaction mixture was concentrated in vacuo. The yellow slurry was dissolved in methylene chloride (10 mL) and then cooled to 0° C. To this solution was added a mixture of (5-amino-pyrazin-2-yl)-acetonitrile (268.9 mg, 2.004 mmol) and pyridine (324 μL, 4.009 mmol) in methylene chloride (10 mL). The reaction mixture was stirred at 0° C. for 30 min and then warmed to 25° C. where it was stirred for 16 h. The reaction mixture was then diluted with methylene chloride (100 mL) and water (50 mL). The organic layer was washed with a 1N aqueous hydrochloric acid solution (50 mL), a saturated aqueous sodium bicarbonate solution (50 mL), and a saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 1/9 ethyl acetate/methylene chloride) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyanomethyl-pyrazin-2-yl)-3-cyclopentyl-propionamide (523.4 mg, 58%) as a white foam: mp 79–82° C. (foam to gel); (ES)+-HRMS m/e calcd for C21H23ClN4O3S (M+H)+ 447.1252, found 447.1255.

Provenance & Evidence