反应详情

Phenyl N-(4-(6-carbamoyl-7-methoxy-4-quinolyl)oxy-2-chlorophenyl)carbamate (17.5 g, 37.7 mmol) disclosed in WO 02/32872 was dissolved in N,N-dimethylformamide (350 mL), and then cyclopropylamine (6.53 mL, 94.25 mmol) was added to the reaction mixture under a nitrogen atmosphere, followed by stirring overnight at room temperature. To the mixture was added water (1.75 L), and the mixture was stirred. Precipitated crude crystals were collected by filtration, washed with water, and dried at 70° C. for 50 min. To the obtained crude crystals was added ethanol (300 mL), and then the mixture was heated under reflux for 30 min to dissolve, followed by stirring overnight to cool slowly down to room temperature. Precipitated crystals was collected by filtration and dried under vacuum, and then further dried at 70° C. for 8 hours to give the titled crystals (12.91 g; 80.2%).

1. stirringthe mixture was stirred
2. customPrecipitated crude crystals
3. filtrationwere collected by filtration
4. washwashed with water
5. customdried at 70° C. for 50 min
6. customTo the obtained crude crystals
7. temperaturethe mixture was heated
8. temperatureunder reflux for 30 min
9. dissolutionto dissolve
10. stirringby stirring overnight
11. temperatureto cool slowly down to room temperature
12. customPrecipitated crystals
13. filtrationwas collected by filtration
14. customdried under vacuum
15. customfurther dried at 70° C. for 8 hours
16. customto give the titled crystals (12.91 g; 80.2%)