反应详情

温度

95 °C

A solution of 4-chloro-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazoline (1.22 g, 3.65 mmol), (prepared as described for the starting material in Example 241), 4-fluoro-5-hydroxy-2-methylindole (723 mg, 4.38 mmol), (prepared as described for the starting material in Example 237), in DMF (20 ml) containing potassium carbonate (756 mg, 5.48 mmol) was stirred at 95° C. for 3 hours. After cooling, the mixture was filtered and the filtrate was evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (9/1) followed by methylene chloride/methanol/methanol saturated with ammonia (90/5/5). The fractions containing the expected product were combined and evaporated. The residue was triturated with ether, filtered, washed with ether and dried under vacuum. The solid was dissolved in methylene chloride/ethyl acetate and the minimum of methanol, filtered and the volatiles were removed under vacuum. The solid was triturated with ether, filtered, washed with ether and dried under vacuum at 50° C. to give 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazoline (1.06 g, 62%).

1. custom(prepared
2. temperatureAfter cooling
3. filtrationthe mixture was filtered
4. customthe filtrate was evaporated
5. customThe residue was purified by column chromatography
6. washeluting with methylene chloride/methanol (9/1)
7. additionThe fractions containing the expected product
8. customevaporated
9. customThe residue was triturated with ether
10. filtrationfiltered
11. washwashed with ether
12. customdried under vacuum
13. dissolutionThe solid was dissolved in methylene chloride/ethyl acetate
14. filtrationthe minimum of methanol, filtered
15. customthe volatiles were removed under vacuum
16. customThe solid was triturated with ether
17. filtrationfiltered
18. washwashed with ether
19. customdried under vacuum at 50° C.