反应详情

4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-7-hydroxy-6-methoxyquinazoline (300 mg, 0.88 mmol), (prepared as described for the starting material in Example 7), 2-(4-acetylpiperazin-1-yl)ethanol (183 mg, 1.06 mmol) and triphenylphosphine (278 mg, 1.06 mmol) were stirred together in dichloromethane (10 ml) and the mixture cooled in an ice/water bath. Diisopropyl azodicarboxylate (209 μl, 1.06 mmol) was added and the mixture stirred for 1.5 hours. A further one mole equivalent of 2-(4-acetylpiperazin-1-yl)ethanol (172 mg, 1 mmol), triphenylphosphine (262 mg, 1 mmol) and diisopropyl azodicarboxylate (197 μl, 1 mmol) were added and the mixture stirred for a further 1 hour. The volatiles were removed under vacuum and the residue was purified by column chromatography eluting with methylene chloride/methanol (95/5) to give a crude solid that was further purified by preparative HPLC to give 7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (75 mg, 17%).

1. temperaturethe mixture cooled in an ice/water bath
2. stirringthe mixture stirred for a further 1 hour
3. customThe volatiles were removed under vacuum
4. customthe residue was purified by column chromatography
5. washeluting with methylene chloride/methanol (95/5)
6. customto give a crude solid that
7. customwas further purified by preparative HPLC