反应详情

7-(3-(1,1-Dioxothiomorpholino)propoxy)-6-methoxy-3,4-dihydroquinazolin-4-one (4.2 g, 11.4 mmol) was suspended in thionyl chloride (45 ml) and DMF (0.1 ml) then heated at reflux for 2.5 hours. The residue was diluted with toluene, the thionyl chloride was evaporated under vacuum, the residue was then azeotroped with toluene three times. The residue was taken up in water and basified (pH8) with saturated aqueous sodium hydrogen carbonate solution. The aqueous layer was extracted with dichloromethane (×4), the organic layer was washed with water and brine then filtered through phase separating paper. The organic layer was concentrated under vacuum to give an orange solid. The solid was flash chromatographed on silica eluting with dichloromethane and methanol (95/5). The relevant fractions were combined and evaporated to give a solid which was triturated with ether then filtered and dried to give 4-chloro-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline (2.27 g, 52%).

1. temperatureat reflux for 2.5 hours
2. customthe thionyl chloride was evaporated under vacuum
3. customthe residue was then azeotroped with toluene three times
4. extractionThe aqueous layer was extracted with dichloromethane (×4)
5. washthe organic layer was washed with water and brine
6. filtrationthen filtered through phase
7. customseparating paper
8. concentrationThe organic layer was concentrated under vacuum
9. customto give an orange solid
10. customchromatographed on silica eluting with dichloromethane and methanol (95/5)
11. customevaporated
12. customto give a solid which
13. customwas triturated with ether
14. filtrationthen filtered
15. customdried