反应详情

4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(piperidin-4-ylmethoxy)quinazoline (180 mg, 0.41 mmol), (prepared as described for the starting material in Example 11), was suspended in tetrahydrofuran (15 ml), and diisopropylethylamine (108 μl, 0.45 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulphonate (98 mg, 0.62 mmol) were added. The mixture was heated at reflux for 1.5 hours. Diisopropylethylamine (36 μl, 0.21 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulphonate (45 mg, 0.21 mmol) were added and the mixture was heated at reflux for a further 2 hours. The mixture was concentrated under reduced pressure and column chromatography of the residue, eluting with 1% methanol/methylene chloride gave a sticky solid. This was triturated with diethyl ether and filtered to give 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[1-(2,2,2-trifluoroethyl)piperidin-4-ylmethoxy]quinazoline (93 mg, 44%).

1. temperatureThe mixture was heated
2. temperatureat reflux for 1.5 hours
3. temperaturethe mixture was heated
4. temperatureat reflux for a further 2 hours
5. concentrationThe mixture was concentrated under reduced pressure and column chromatography of the residue
6. washeluting with 1% methanol/methylene chloride
7. customgave a sticky solid
8. customThis was triturated with diethyl ether
9. filtrationfiltered