2-Aminothiazole → (E)-3-cycloheptyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-thiazol-2-yl-acrylamide

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (341 mg, 1.3 mmol) in methylene chloride (7 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (231 mg, 1.3 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with (E)-3-cycloheptyl-2-(4-(methanesulfonyl)-3-(trifluoromethyl)-phenyl)-acrylic acid (255 mg, 0.65 mmol). After 15 min at 0° C., the reaction mixture became clear. The clear solution was then allowed to warm to 25° C. where it was stirred for 1.5 h. The reaction mixture was then treated with 2-aminothiazole (193 mg, 1.95 mmol), and the resulting suspension was stirred for 2 d at 25° C. The reaction mixture was concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (50 mL) and a 1N aqueous hydrochloric acid solution (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30) 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). The organic layer was then dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 4/1 to 2/1 hexanes/ethyl acetate) afforded the pure (E)-3-cycloheptyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-thiazol-2-yl-acrylamide (133 mg, 43%) as an amorphous solid.

Provenance & Evidence