Potassium Carbonate → 4-(3-{4-[(2E)-3-(2,5-Difluorophenyl)prop-2-en-1-yl]piperazin-1-yl}propyl)-6-methoxy-2H-1,4-benzoxazin-3(4H)-one

Participants

Reaction Conditions

Reaction Steps

A solution of 6-methoxy-4-(3-piperazin-1-ylpropyl)-2H-1,4-benzoxazin-3(4H)-one trifluoroacetate (Intermediate 118, 985 mg, 1.52 mmol) in dry ethanol (10 mL) was converted to the free base with N,N-diisopropylethylamine for 30 min and then was added 2-[(1E)-4-chloroprop-1-en-1-yl]-1,4-difluorobenzene (Intermediate 124, 315 mg, 1.67 mmol), and potassium carbonate (230 mg, 1.67 mmol). The mixture was heated at 80° C. for 18 hours, cooled to room temperature and then concentrated to dryness under reduced pressure. The residue was partitioned between water (50 mL) and dichloromethane (100 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure. Chromatography on silica gel with dichloromethane/methanol (95:5) gave the free base of the title compound as a yellow foam. The free base was taken up in dichloromethane (14 mL), followed by the addition of 2M HCl in ether (0.41 mL). The precipitate was collected by filtration and to give the bis hydrochloride salt of the product as a colorless solid, 171 mg (79%).

Provenance & Evidence