Pyridine → HCID 67483235, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid (8.32 g, 20.0 mmol) in methylene chloride (100 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (11.14 mL, 22.28 mmol) and N,N-dimethylformamide (0.5 mL). The reaction mixture was stirred at 0° C. for 45 min and at 25° C. for 1 h. The reaction mixture was then cooled to 0° C. and treated with a solution of 4-aminopyrimidine (4.02 g, 4.28 mmol) in tetrahydrofuran (60 mL) followed by pyridine (6.0 mL, 74.2 mmol). This solution was stirred at 0° C. for 15 min and at 25° C. for 16 h. At this time, the reaction was poured onto a slurry of ice water (100 g) and then extracted with ethyl acetate (3×250 mL) and ether (1×200 mL). The combined organic layers were washed with water (1×500 mL) and a saturated aqueous sodium chloride solution (3×300 mL). The organic layer was then dried over sodium sulfate and magnesium sulfate, treated with charcoal, filtered through a pad of celite, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-pyrimidin-4-yl-propionamide (6.36 g, 72.1%) as a white solid: mp 85-90° C.; [α]23589=−32.53° (c=0.166, chloroform); EI-HRMS m/e calcd for C20H22F3N3O3S (M+) 441.1334, found 441.1333.

Provenance & Evidence