Pyridine → HCID 21959027, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methylsulfonyl-phenyl)-N-methyl-N-(1(R)-methyl-2-oxo-2(R)-phenyl-ethyl)-3-(2-oxo-cyclopentyl)-propionamide (1.29 g, 2.63 mmol) in dioxane (4.43 mL) was treated with an 18M aqueous hydrochloric acid solution (4.43 mL). The reaction was then heated to 120° C. for 18 h. At this time, the reaction was cooled to 25° C., diluted with water (50 mL), and extracted with a 90/10 methylene chloride/methanol solution (3×100 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, ethyl acetate) afforded racemic 2-(3-chloro-4-methylsulfonyl-phenyl)-3-(2-oxo-cylopentyl)-propionic acid (563.3 mg, 62.1%) as a light tan foam. A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(2-oxo-cyclopentyl)-propionic acid (563.3 mg, 1.6 mmol) in methylene chloride (16.4 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.90 mL, 1.80 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 10 min and at 25° C. for 20 min. The reaction mixture was then treated with a solution of 2-aminopyrazine (342 mg, 3.60 mmol) and pyridine (0.3 mL, 3.60 mmol) in tetrahydrofuran (8.2 mL). This solution was stirred at 25° C. for 18 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in methylene chloride (100 mL) and washed with a 1N aqueous hydrochloric acid solution (2×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 75/25 ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(2-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide (198.8 mg, 28.9%) as a clear oil.

Provenance & Evidence