反应详情

温度

90 °C

A mixture of 7-(1-(tert-butoxycarbonyl)piperidin-4-ylmethoxy)4chloro-6-methoxycinnoline (204 mg, 0.5 mmol), 5-hydroxy-2-methylindole (81 mg) and cesium carbonate (326 mg, 1 mmol) in DMF (2.5 ml) was stirred at 90° C. for 2 hours. After cooling, the mixture was filtered, wash ed with DMF and the volatiles were removed under vacuum. The crude product was dissolved in methylene chloride (4 ml) containing TEA (1.5 ml) and was stirred at ambient temperature for 1 hour. The volatiles were removed under vacuum. The residue was partitioned between methylene chloride and 1N aqueous sodium hydroxide. The organic layer was separated, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography eluting with a gradient of methylene chloride/methanol saturated with ammonia (5/95 to 15/85). The fractions containing the expected product were combined and evaporated. The residue was triturated under diethyl ether and the precipitate was filtered, washed with ether and dried under vacuum to give 7-(1-tert-butoxycarbonylpiperidin-4-ylmethoxy)-6-methoxy-4-(2-methylindol-5yl)cinnoline (42 mg, 20%).

1. temperatureAfter cooling
2. filtrationthe mixture was filtered
3. washwash
4. customthe volatiles were removed under vacuum
5. dissolutionThe crude product was dissolved in methylene chloride (4 ml)
6. additioncontaining TEA (1.5 ml)
7. stirringwas stirred at ambient temperature for 1 hour
8. customThe volatiles were removed under vacuum
9. customThe residue was partitioned between methylene chloride and 1N aqueous sodium hydroxide
10. customThe organic layer was separated
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. customevaporated
14. customThe residue was purified by column chromatography
15. washeluting with a gradient of methylene chloride/methanol saturated with ammonia (5/95 to 15/85)
16. additionThe fractions containing the expected product
17. customevaporated
18. customThe residue was triturated under diethyl ether
19. filtrationthe precipitate was filtered
20. washwashed with ether
21. customdried under vacuum