Pyridine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-methanesulfonylamino-pyridin-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, 224 mg, 0.67 mmol) in methylene chloride was cooled to 0° C. and then was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.37 mL, 0.74 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 N-(6-amino-pyridin-3-yl)-methanesulfonamide (190 mg, 1.01 mmol) and pyridine (0.08 mL, 1.01 mmol) in tetrahydrofuran (3.38 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 the organic layer 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 then dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 3/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-methanesulfonylamino-pyridin-2-yl)-propionamide (34.4 mg, 10.2%) as a light tan solid: mp 146–150° C.; EI-HRMS m/e calcd for C21H26ClN3O5S2 (M+H)+ 500.1075, found 500.1081.

Provenance & Evidence