Pyridine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclo-pentyl-N-(5-methanesulfonylamino-pyrazin-2-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 482 mg, 1.45 mmol) in methylene chloride (14.6 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.80 mL, 1.60 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 30 min. The reaction mixture was then treated with a solution of N-(5-amino-pyrazin-2-yl)-methanesulfonamide (548.8 mg, 2.91 mmol) and pyridine (0.24 mL, 2.91 mmol) in tetrahydrofuran (7.29 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 (50 mL) and was washed consecutively with a 1N aqueous hydrochloric acid solution (1×100 mL) and a saturated aqueous sodium bicarbonate solution (1×100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 95/5 methylene chloride/methanol) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclo-pentyl-N-(5-methanesulfonylamino-pyrazin-2-yl)-propionamide (43.0 mg, 5.9%) as an off-white solid: mp 108–110° C.; EI-HRMS m/e calcd for C20H25ClN4O5S2 (M+H)+ 501.1028, found 501.1031.

Provenance & Evidence