Dimethylformamide → 4-Chloro-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline

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Reaction Steps

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%).

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