2-Aminothiazole → (E)-3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-N-thiazol-2-yl-acrylamide

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (204 mg, 0.78 mmol) in methylene chloride (8 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (138 mg, 0.78 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of (E)-3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-acrylic acid (143 mg, 0.39 mmol) in methylene chloride (5 mL). The reaction mixture was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 1.5 h. The reaction mixture was then treated with 2-aminothiazole (117 mg, 1.17 mmol), and the resulting suspension was stirred for 2 d at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (20 mL) and a 1N aqueous hydrochloric acid solution (30 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×15 mL). The combined organic extracts were successively washed with a 1N aqueous hydrochloric acid solution (1×50 mL), 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, 1/2 hexanes/ethyl acetate) afforded the (E)-3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-N-thiazol-2-yl-acrylamide (27 mg, 15.5%) as an amorphous white solid: EI-HRMS m/e calcd for C20H19F3N6OS (M+) 448.1293, found 448.1285.

Provenance & Evidence