Hydrochloric Acid → Tivozanib hydrochloride anhydrous

Participants

Reaction Steps

N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea (2 g) produced in Production Example was added to and was completely dissolved in N,N-dimethylformamide (10 mL) at 80° C. The solution was allowed to cool to room temperature, and 12 N hydrochloric acid (202 mL) was then added thereto, followed by stirring for one hr. The reaction solution was heated to 80° C., 1-propanol (60 mL) of 80° C. was added thereto, and the mixture was stirred at 80° C. After the precipitation of crystals was confirmed, the solution was cooled to 5° C. and was stirred at that temperature overnight. The resultant precipitate was collected by filtration, and the filtered product was dried under the reduced pressure to give a form II crystal of N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea hydrochloride (1.81 g, yield 83.8%).

Provenance & Evidence