2-Aminothiazole → HCID 9884201, compound

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (1.23 g, 4.7 mmol) in methylene chloride (15 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (836 mg, 4.7 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of (E)-2-(4-(methanesulfonyl)-phenyl)-pentenoic acid (703 mg, 2.76 mmol) in methylene chloride (5 mL). The clear solution was stirred for 10 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 (829 mg, 8.28 mmol), and the resulting suspension was stirred for 15 h at 25° C. The reaction mixture was then 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 saturated aqueous sodium bicarbonate solution (2×50 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 4/1 to 1/1 hexanes/ethyl acetate) afforded (E)-2-(4-methanesulfonyl-phenyl)-pent-2-enoic acid thiazol-2-ylamide (150 mg, 16%) as crystalline solid: mp 155-158° C.; EI-HRMS m/e calcd for C15H16N2O3S2 (M+) 336.0602, found 336.0601.

Provenance & Evidence