2,6-Lutidine → N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (1.00 g, 3.023 mmol) in methylene chloride (16 mL) was cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (1.15 mL, 13.18 mmol) followed by N,N-dimethylformamide (2 drops). The reaction mixture was stirred at 0° C. for 20 min and then at 25° C. for 2 h. The solution was then concentrated in vacuo. The residue was dissolved in methylene chloride (16 mL) and cooled to 0° C. To this solution was added a solution of 2-amino-5-bromopyrazine (530.0 mg, 3.046 mmol) and 2,6-lutidine (420 μL, 3.606 mmol) in tetrahydrofuran (16 mL) over 1 min. The reaction mixture was stirred at 0° C. for 30 min and then at 25° C. for 3 h. The reaction material was then diluted with ethyl acetate and washed with a 1N aqueous hydrochloric acid solution. The aqueous layer was back-extracted with a 1N aqueous hydrochloric acid solution. The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 1/3 ethyl acetate/hexanes) afforded N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (1.00 g, 68%) as a white foam: (ES)+-HRMS m/e calcd for C19H21BrClN3O3S (M+H)+ 486.0249, found 486.0254.

Provenance & Evidence