反应详情

温度

95 °C

A solution of 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (1.76 g, 5.47 mmol), (prepared as described for the starting material in Example 9), 4-fluoro-5-hydroxyindole (0.992 g, 6.57 mmol), (prepared as described for the starting material in Example 242), in DMF (25 ml) containing potassium carbonate (1.14 g; 8.21 mmol) was heated at 95° C. for 1 hour. After cooling, the mixture was filtered and washed with DMF. The filtrate was evaporated and the residue was purified by column chromatography eluting with methanol/methylene chloride (1/9) followed by methanol/methanol chloride/methanol (containing ammonia) (16/80/4). The fractions containing the expected product were combined and evaporated. The residue was repurified by column chromatography eluting with a gradient of methylene chloride/methanol (80/20 to 40/60). The fractions containing the expected product were combined and evaporated. The residue was triturated in cold methanol and the solid was filtered, washed with ether and dried under vacuum to give 4-(4-fluoroindol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (1.24 g, 52%).

1. custom(prepared
2. temperatureAfter cooling
3. filtrationthe mixture was filtered
4. washwashed with DMF
5. customThe filtrate was evaporated
6. customthe residue was purified by column chromatography
7. washeluting with methanol/methylene chloride (1/9)
8. additionThe fractions containing the expected product
9. customevaporated
10. customThe residue was repurified by column chromatography
11. washeluting with a gradient of methylene chloride/methanol (80/20 to 40/60)
12. additionThe fractions containing the expected product
13. customevaporated
14. customThe residue was triturated in cold methanol
15. filtrationthe solid was filtered
16. washwashed with ether
17. customdried under vacuum