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

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (8.79 g, 33.52 mmol) in methylene chloride (100 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (5.97 g, 33.52 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)-phenyl)-acrylic acid (5.17 g, 16.76 mmol) in methylene chloride (20 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 (5.04 g, 50.3 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 (250 mL) and a 1N aqueous hydrochloric acid solution (150 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×100 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) and a saturated aqueous sodium chloride solution (1×250 mL), dried over anhydrous magnesium sulfate, filtered, and, concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 8.5/1.5 to 3/2 hexanes/ethyl acetate) afforded (E)-3-cyclohexyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-acrylamide (2.8 g, 42%) as an amorphous solid: mp 167-1694° C.; EI-HRMS m/e calcd for C19H22O3S2 (M+) 390.1072, found 390.1073.

Provenance & Evidence