2,6-Lutidine → N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 262.9 mg, 0.79 mmol) in methylene chloride (4 mL) was cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (275 μL, 3.15 mmol) and N,N-dimethylformamide (2 drops). The reaction mixture was stirred at 0° C. for 30 min and then slowly allowed to warm to 25° C. where it was stirred for 2.5 h. The solution was then concentrated in vacuo to remove solvents. The resulting residue was dissolved in methylene chloride (3 mL) and then cooled to 0° C. This cooled solution was then treated dropwise with a solution of 1-(5-amino-pyrazin-2-yl)-ethanone O-tert-butyl-oxime (150.2 mg, 0.72 mmol) and 2,6-lutidine (100 μL) in tetrahydrofuran (4 mL), followed by quick rinse with methylene chloride (1 mL). The reaction mixture was stirred at 0° C. for 30 min and then was allowed to warm to 25° C. where it was stirred overnight. The reaction mixture was then quenched with water and stirred at 25° C. for 30 min. The reaction mixture was then diluted with ethyl acetate (300 mL) and a 1N aqueous citric acid solution (300 mL), and the layers were shaken and separated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×300 mL), water (1×300 mL), and a saturated aqueous sodium chloride solution (1×300 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 1/3 ethyl acetate/hexanes) afforded the N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (216.5 mg, 58%) as a white foam: mp 95.7–99.9° C. (foam to gel); (ES)+-HRMS m/e calcd for C25H33ClN4O4S (M+H)+ 521.1984, found 521.1994.

Provenance & Evidence