2-Aminothiazole → HCID 10158899, compound

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (236 mg, 0.9 mmol) in methylene chloride (6 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (160 mg, 0.9 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with the 2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cyclopentyl-propionic acid (151 mg, 0.45 mmol). The clear solution was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 2 h. The reaction mixture was then treated with 2-aminothiazole (135 mg, 1.35 mmol), and the resulting suspension was stirred for 20 h at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (30 mL) and a 1N 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 hexanes/ethyl acetate) afforded 2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cyclopentyl-N-thiazol-2-yl-propionamide (80 mg, 42%) as a white solid: mp 190-193° C.; EI-HRMS m/e calcd for C19H21ClN6OS (M+) 416.1186, found 416.1183.

Provenance & Evidence