反应详情

A mixture of 6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one (260 mg, 0.90 mmol), thionyl chloride (5 ml) and DMF (2 drops) was heated at reflux for 45 minutes and allowed to cool. The excess thionyl chloride was removed by evaporation, and the residue azeotroped with toluene. A solution of 4-chloro-2-fluoro-5-hydroxyaniline (160 mg, 1.0 mmol), (as described in EP 61741 A2), in isopropanol (5 ml) was added to the residue and the mixture was heated at reflux for 1 hour and then allowed to cool. The mixture was diluted with acetone, and the solid product collected by filtration, washed with acetone and dried to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochloride(381 mg, 83%).

1. temperaturewas heated
2. temperatureat reflux for 45 minutes
3. temperatureto cool
4. customThe excess thionyl chloride was removed by evaporation
5. customthe residue azeotroped with toluene
6. temperaturethe mixture was heated
7. temperatureat reflux for 1 hour
8. temperatureto cool
9. filtrationthe solid product collected by filtration
10. washwashed with acetone
11. customdried