反应详情

温度

90 °C

Reduced iron (84.2 g, 1.51 mol) and 1.5 mol/L hydrochloric acid (605 mL) were added to ethanol (2.5 L) and the mixture was heated to 90° C. with stirring. To this mixture was added (7-bromo-6-nitro-4-quinazolinyl)-(3-chloro-4-fluorophenyl)amine 4 times (30 g each time) every 30 min. The mixture was heated under reflux for 5 hrs and the inner temperature was set to 50° C. 2N Aqueous sodium hydroxide solution (450 mL) and 1N aqueous sodium hydroxide solution were added to adjust the pH thereof to 7-8 and the mixture was stirred for a while. Ethyl acetate (1 L) and Celite (300 g) were added, and after stirring for a while, the mixture was filtered through Celite. The residue was washed with THF-ethyl acetate (1:1, 1 L) and the filtrate was concentrated under reduced pressure. Water (1 L) was added to the concentrate and the product was collected by filtration and dried under reduced pressure at 60° C. overnight to give the title compound (108.76 g, 98%).

1. temperatureThe mixture was heated
2. temperatureunder reflux for 5 hrs
3. customwas set to 50° C
4. stirringto 7-8 and the mixture was stirred for a while
5. stirringafter stirring for a while
6. filtrationthe mixture was filtered through Celite
7. washThe residue was washed with THF-ethyl acetate (1:1, 1 L)
8. concentrationthe filtrate was concentrated under reduced pressure
9. additionWater (1 L) was added to the
10. concentrationconcentrate
11. filtrationthe product was collected by filtration
12. customdried under reduced pressure at 60° C. overnight