反应详情

温度

85 °C

1-Prop-2-ynylpiperazine diTFA salt (329 mg, 0.94 mmol) and potassium carbonate (258 mg, 1.87 mmol) were added to a solution of 7-(3-bromopropoxy)-4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxyquinazoline (144 mg, 0.31 mmol), (prepared as described for the starting material in Example 7), in DMA (3.6 ml). The reaction mixture was stirred at 85° C. overnight before being filtered. The filtrate was concentrated under vacuum and the crude product was purified by column chromatography eluting with increasingly polar mixtures of ammonia/methanol in methylene chloride (1 to 7%). A second purification by column chromatography eluting with a mixture of methanol in methylene chloride (1/9) gave 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-(3-[4-(2-propynyl)piperazin-1-yl]propoxy}quinazoline as a white solid (115 mg, 73%).

1. custom(prepared
2. filtrationbefore being filtered
3. concentrationThe filtrate was concentrated under vacuum
4. customthe crude product was purified by column chromatography
5. washeluting
6. temperaturewith increasingly polar mixtures of ammonia/methanol in methylene chloride (1 to 7%)
7. customA second purification by column chromatography
8. washeluting with a mixture of methanol in methylene chloride (1/9)