反应详情

温度

95 °C

A mixture of 7-benzyloxy-4-chloro-6-methoxy cinnoline (2 g, 6.66 mmol), (prepared as described for the starting material in Example 1), 4-fluoro-5-hydroxy-2-methylindole (1.32 g, 7.99 mmol), (prepared as described for the starting material in Example 1), and cesium carbonate (3.2 g, 9.98 mmol) in DMF (40 ml) was heated at 95° C. for 1.5 hours. 4-Fluoro-5-hydroxy-2-methylindole (82 mg, 0.5 mmol) and cesium carbonate (3.2 g, 9.98 mmol) were added. The mixture was stirred for 1.5 hours at 115° C. The mixture was cooled, the solid was filtered and the filtrate was evaporated under vacuum. The residue was purified by column chromatography, eluting with methylene chloride/ethyl acetate (90/10 followed by 80/20) followed by methylene chloride/ethyl acetate/methanol (80/18/2). The fractions containing the expected product were combined and evaporated and the residue was triturated with ether/pentane (1/1). The solid was filtered, washed with pentane and dried under vacuum to give 7-benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxycinnoline (1.1 g, 39%).

1. custom(prepared
2. custom(prepared
3. temperatureThe mixture was cooled
4. filtrationthe solid was filtered
5. customthe filtrate was evaporated under vacuum
6. customThe residue was purified by column chromatography
7. washeluting with methylene chloride/ethyl acetate (90/10 followed by 80/20)
8. additionThe fractions containing the expected product
9. customevaporated
10. customthe residue was triturated with ether/pentane (1/1)
11. filtrationThe solid was filtered
12. washwashed with pentane
13. customdried under vacuum