Dimethylformamide → 4-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)[N:9]=[CH:8][NH:7][C:6]2=O.CN(C=O)C.S(Cl)([Cl:31])=O>>[Cl:31][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1Participants
Procedure
6-Methoxy-7-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one (23.9 g, 75 mmol) was suspended in thionyl chloride (210 ml) and DMF (1.8 ml) then heated at reflux for 1.5 hours. The thionyl chloride was removed by evaporation under vacuum and the residue 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 (4×400 ml), the organic layer was washed with water and brine then dried (MgSO4). After filtration the organic layer was concentrated under vacuum to give a yellow solid which was triturated with ethyl acetate to give 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (17.39 g, 52%) as a pale cream solid.
Workup
- temperatureat reflux for 1.5 hours
- customThe thionyl chloride was removed by evaporation under vacuum
- customthe residue azeotroped with toluene three times
- extractionThe aqueous layer was extracted with dichloromethane (4×400 ml)
- washthe organic layer was washed with water and brine
- dry with materialthen dried (MgSO4)
- filtrationAfter filtration the organic layer
- concentrationwas concentrated under vacuum
- customto give a yellow solid which
- customwas triturated with ethyl acetate
Sources & evidence
- ORD record
- ord-81f52370a5a846aa8d7be8314f5ebf61
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08492560B2
Reaction notes
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