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

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (1.39 g, 5.3 mmol) in methylene chloride (50 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (0.94 g, 5.3 mmol). The reaction mixture was stirred at 0° C. For 30 min and then treated with a solution of (E)-3-cyclohexyl-2-(4-(methanesulfonyl)-3-(trifluoromethyl)-phenyl)-acrylic acid (1.00 g, 2.66 mmol) in methylene chloride (10 mL). The clear solution 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 (800 mg, 7.98 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 (100 mL) and a 1N aqueous hydrochloric acid solution (100 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×50 mL). The combined organic extracts were successively washed with a 1N aqueous hydrochloric acid solution (1×100 mL), a saturated aqueous sodium bicarbonate solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organic layer was then dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 5/1 to 3/2 hexanes/ethyl acetate) afforded the (E)-3-cyclohexyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-thiazol-2-yl-acrylamide (367 mg, 30%) as an amorphous solid: EI-HRMS m/e calcd for C20H21F3N2O3S2 (M+) 458.0946, found 458.0947.

Provenance & Evidence