Triethylamine → HCID 86671250, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-3-tert-Butoxycarbonylamino-2-({2-[2-(3-hydroxy-phenyl)-acetylamino]-4-methyl-thiazole-5-carbonyl}-amino)-propionic acid methyl ester (150 mg, 0.305 mmol) in 4M HCl in dioxane (6 mL, 24 mmol) was stirred at 25° C. for 2 h. The reaction mixture was concentrated under reduced pressure. To the reaction solid was added ethyl ether (2×50) followed by concentrating under reduced pressure to give a white solid, which was dissolved in the anhydrous DMF (6 mL). To this solution was added HBTU (174 mg, 0.459 mmol), HOBt (61 mg, 0.451 mmol), 3,5-difluorobenzoic acid (60 mg, 0.379 mmol) and triethylamine (0.16 mL, 1.148 mmol). The solution was allowed to stir at 25° C. for 2 h and concentrated under reduced pressure to remove most of the DMF. The reaction was then diluted with ethyl acetate (100 mL), washed with water (20 mL), followed by aqueous 1N HCl (20 mL) and then brine (20 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (40%-100% EtOAc in hexanes) to give (S)-3-(3,5-Difluoro-benzoylamino)-2-({2-[2-(3-hydroxy-phenyl)-acetylamino]-4-methyl-thiazole-5-carbonyl}-amino)-propionic acid methyl ester (92.5 mg, 57%) as a white foam. MS m/e 533.5 (M+H+).

Provenance & Evidence