2-Aminothiazole → 3-cyclopentyl-2-[4-(3-hydroxy-prop-1-ynyl)-phenyl]-N-thiazol-2-yl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2-[4-(3-hydroxy-prop-1-ynyl)-phenyl]-propionic acid (380 mg, 1.4 mmol), in methylene chloride (4 mL) and N,N-dimethylformamide (1 drop) at 0° C. was treated with oxalyl chloride (1.22 mL, 14.0 mmol). The reaction was warmed to 25° C. and stirred at 25° C. for 18 h. At this time, the reaction mixture was concentrated in vacuo. The resulting residue was dissolved in methylene chloride (4 mL) and added to a solution of 2-aminothiazole (280 mg, 2.79 mmol) and N,N-diisopropylethylamine (0.50 mL, 2.87 mmol) in methylene chloride (8 mL) at 25° C. The reaction was stirred at 25° C. for 18 h. At this time, the reaction was concentrated in vacuo. The residue was poured into a 0.5N aqueous hydrochloric acid solution (50 mL) and extracted into ethyl acetate (1×100 mL). The organic extract was washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a half-saturated aqueous sodium chloride solution (1×50 mL). The aqueous layer was back extracted with ethyl acetate (1×100 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 60/40 hexanes/ethyl acetate) afforded the 3-cyclopentyl-2-[4-(3-hydroxy-prop-1-ynyl)-phenyl]-N-thiazol-2-yl-propionamide (159 mg, 72%) as an off-white solid: mp 220-222° C.; EI-HRMS m/e calcd for C20H22N2O2S (M+) 354.1402, found 354.1388.

Provenance & Evidence