Triethylamine → 2-(3,5-dichloro-1H-1,2,4-triazol-1-yl)-1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-ethanone

Participants

Reaction Steps

A mixture of 3,5-dichloro-1H-1,2,4-triazole-1-acetic acid (i.e. the product of Example 16, Step B), (114 mg, 0.58 mmol) in thionyl chloride (5 mL) was heated at reflux for 1 h. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. The resulting crude acid chloride was dissolved in dichloromethane (5 mL) and added to a solution of 4-[4-[4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl]-2-thiazolyl]piperidine hydrochloride (196 mg, 0.51 mmol) and triethylamine (0.5 mL) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 3 h, diluted with dichloromethane, washed with 1 N hydrochloric acid, aqueous sodium chloride, and dried (MgSO4). The reaction mixture was concentrated under reduced pressure and further purified by medium-pressure liquid chromatography to give 80 mg of the title product as a white solid melting at 147-150° C.

Provenance & Evidence