反应详情

A mixture of 6-methoxy-7-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one (370 mg, 1.16 mmol), thionyl chloride (5 ml) and DMF (3 drops) was heated at reflux for 2 hours and allowed to cool. The excess thionyl chloride was removed by evaporation and the residue was azeotroped with toluene. A solution of 2-fluoro-5-hydroxy-4-methylaniline (220 mg, 1.56 mmol) in isopropanol (10 ml) was added to the solid residue and the mixture was heated at reflux for 2 hours and then allowed to cool. The resulting precipitate was collected by filtration, washed with methylene chloride and dried. The impure solid product was treated with aqueous sodium hydrogen carbonate, to give a suspension and the product was recollected by filtration and purified by column chromatography eluting with methylene chloride/methanol (9/1) to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (140 mg, 27%).

1. temperaturewas heated
2. temperatureat reflux for 2 hours
3. temperatureto cool
4. customThe excess thionyl chloride was removed by evaporation
5. customthe residue was azeotroped with toluene
6. temperaturethe mixture was heated
7. temperatureat reflux for 2 hours
8. temperatureto cool
9. filtrationThe resulting precipitate was collected by filtration
10. washwashed with methylene chloride
11. customdried
12. additionThe impure solid product was treated with aqueous sodium hydrogen carbonate
13. customto give a suspension
14. filtrationthe product was recollected by filtration
15. custompurified by column chromatography
16. washeluting with methylene chloride/methanol (9/1)