Pyridine → HCID 10097331, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-propionic acid (prepared as in Example 1, 136 mg, 0.41 mmol) in methylene chloride (5 mL) and N,N-dimethylformamide (2 drops) was cooled to 5° C. and then treated with oxalyl chloride (75 μL, 0.86 mmol). The mixture was stirred at 5° C. for 5 min, the cooling bath was removed, and the mixture stirred an additional 10 min. The solvent was concentrated in vacuo. The residue was dissolved in benzene (10 mL), and the solvent again concentrated in vacuo. The resulting acid chloride was dissolved in methylene chloride (5 mL), cooled to 0° C., and then treated with a solution of 5-(2,2-dimethoxy-ethyl)-pyrazin-2-ylamine (75 mg, 0.41 mmol) and pyridine (85 μL, 1.05 mmol) methylene chloride (5 mL). The reaction mixture was stirred at 0° C. for 5 min, the cooling bath was removed, and the stirring was continued for 18 h. The mixture was diluted with methylene chloride (25 mL), and the solution was washed consecutively with a saturated aqueous sodium bicarbonate solution (25 mL), a 0.5M aqueous hydrochloric acid solution, and a saturated aqueous sodium chloride solution (25 mL). Each aqueous wash was back-extracted with another small portion 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, eluted with 1/3 to 1/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2,2-dimethoxy-ethyl)-pyrazin-2-yl]-propionamide (120 mg, 59%): (ES)+-HRMS m/e calcd for C23H30ClN3O5S (M+H)+ 496.1668, found 496.1672.

Provenance & Evidence