反应详情

1M Ethereal hydrogen chloride (0.72 ml, 0.72 mmol) was added to 4-chloro-6-methoxy-7-(2-morpholinoethoxy)quinazoline (210 mg, 0.65 mmol) and 4-chloro-2-fluoro-5-hydroxyaniline (115 mg, 0.71 mmol), (as described in EP 61741 A2), in isopropanol (5 ml) and the mixture heated at reflux for 2 hours and then allowed to cool. The mixture was diluted with acetone and the precipitated product collected by filtration. The impure product was dissolved in methylene chloride/ammonia (100/1) and methanol, the insolubles removed by filtration and the volatiles were removed from the filtrate by evaporation. The solid residue was washed with water and dried to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-morpholinoethoxy)quinazoline (60 mg, 21%).

1. temperaturethe mixture heated
2. temperatureat reflux for 2 hours
3. temperatureto cool
4. filtrationthe precipitated product collected by filtration
5. dissolutionThe impure product was dissolved in methylene chloride/ammonia (100/1)
6. custommethanol, the insolubles removed by filtration
7. customthe volatiles were removed from the filtrate by evaporation
8. washThe solid residue was washed with water
9. customdried