Hydrochloric Acid → 1-{3-Cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-propionyl}-3-methyl-urea

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-propionic acid (368 mg, 1.0 mmol) in fluorobenzene (1.5 mL) and N,N-dimethylformamide (6 liL) at 25° C. was treated dropwise with oxalyl chloride (107.7 μL, 1.21 mmol) over 2-3 min. The clear solution was stirred for 1 h at 25° C. and then treated with methyl urea (322 mg, 2.0 mmol). The resulting suspension was heated at 70° C. (bath temperature) for 10 min and then treated with pyridine (162 liL, 2.0 mmol). The reaction mixture was then stirred at 70° C. for 20 h. The reaction mixture was then cooled to 25° C. and diluted with ethyl acetate (30 mL) and a 3N aqueous hydrochloric acid solution (30 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×20 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 to 1/2 hexanes/ethyl acetate) afforded 1-{3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-propionyl}-3-methyl-urea (338 mg, 80%) as an amorphous white solid: EI-HRMS m/e calcd for C19H23F3N6O2 (M+) 424.1834, found 424.1833.

Provenance & Evidence