反应详情

4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-7-hydroxy-6-methoxyquinazoline (14 g, 41.3 mmol), (prepared as described for the starting material in this example hereinbefore), 3-(4-acetylpiperazin-1-yl)propan-1-ol (9.2 g, 49.5 mmol) and triphenylphosphine (12.9 g, 49.5 mmol) were stirred together in methylene chloride (210 ml). Diisopropyl azodicarboxylate (9.75 ml, 49.5 mmol) was added dropwise and an ice/water bath was used to keep the temperature of the reaction mixture between 15 and 18° C. After the end of addition the reaction mixture was allowed to warm to ambient temperature and stirred for 3 hours. The mixture was filtered and concentrated under reduced pressure and the resulting viscous oil dissolved in acetone (280 ml) and stirred for 45 minutes. The solid that formed was filtered off and dried under vacuum. The solid was purified by chromatography eluting with methylene chloride/methanol (saturated with ammonia) (96/4) to give 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (12.5 g, 60%) as a white solid.

1. customan ice/water bath was used
2. customthe temperature of the reaction mixture between 15 and 18° C
3. additionAfter the end of addition the reaction mixture
4. filtrationThe mixture was filtered
5. concentrationconcentrated under reduced pressure
6. dissolutionthe resulting viscous oil dissolved in acetone (280 ml)
7. stirringstirred for 45 minutes
8. customThe solid that formed
9. filtrationwas filtered off
10. customdried under vacuum
11. customThe solid was purified by chromatography
12. washeluting with methylene chloride/methanol (saturated with ammonia) (96/4)