Pyridine → N-(5-allyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentylpropionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 800.0 mg, 2.418 mmol) in methylene chloride (12 mL) cooled to 0° C. under nitrogen was treated with oxalyl chloride (0.64 mL, 7.336 mmol), followed by N,N-dimethylformamide (2 drops). The reaction mixture was stirred at 0° C. for 20 min and then stirred at 25° C. for 1.25 h. The reaction mixture was concentrated in vacuo. The residue was dissolved in methylene chloride (12 mL), cooled to 0° C. under nitrogen, and then treated with a solution of 5-allyl-pyrazin-2-ylamine (0.37 g, 2.737 mmol) and pyridine (0.59 mL, 7.295 mmol) in methylene chloride (12 mL) over 1 min. The resulting reaction mixture was stirred at 0° C. for 30 min and then at 25° C. for 1 h. The reaction mixture was then diluted with ethyl acetate and washed with a 1N aqueous hydrochloric acid solution. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH, 40L, Silica, 1/1 hexanes/ethyl acetate) afforded N-(5-allyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentylpropionamide (965 mg, 89.1%) as a white foam: LRMS for C22H26ClN3O3S (M−H)+ at m/z=446

Provenance & Evidence