Pyridine → 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-N-(5-vinyl-pyrazin-2-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-pheny)-propionic acid (prepared as in Example 57, 465 mg, 1.5 mmol) in methylene chloride (20 mL) was treated with oxalyl chloride (0.3 mL, 3.4 mmol) and N,N-dimethylformamide (1–2 drops). The solution was stirred at 0° C. for 5 min and then at 25° C. for 15 min. The reaction mixture was concentrated in vacuo. The residue was dissolved in methylene chloride (20 mL), cooled to 0° C., and then treated with a solution of 2-amino-5-vinylpyrazine (prepared as in Example 54, 182 mg, 1.5 mmol) and pyridine (0.37 mL, 4.6 mmol) in methylene chloride (5 mL). The mixture was stirred at 0° C. then stirred at 25° C. overnight. The solution was diluted with methylene chloride (25 mL). The organic layer was washed with a 1N aqueous sodium hydroxide solution (25 mL) and a 1N aqueous hydrochloric acid solution (25 mL). Each aqueous phase was back-extracted with a small volume of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/3 to 1/1 ethyl acetate/hexanes) afforded 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-N-(5-vinyl-pyrazin-2-yl)-propionamide (385 mg, 63%) as a white foam: (ES)+-HRMS m/e calcd for C22H27N3O3S (M+H)+ 414.1846, found 414.1849.

Provenance & Evidence