Dimethylformamide → 4-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline
Reaction equation
CN(C)C=O.[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH2:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)[N:14]=[CH:13][NH:12][C:11]2=O.S(Cl)([Cl:31])=O>>[Cl:31][C:11]1[C:10]2[C:15](=[CH:16][C:17]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[C:8]([O:7][CH3:6])[CH:9]=2)[N:14]=[CH:13][N:12]=1Participants
Procedure
Dimethylformamide (2.0 ml) was added dropwise to a solution of 6-methoxy-7-(3-morpholinopropoxy)-3,4-dihydro-quinazolin-4-one (83.0 g, 261 mmol) in thionyl chloride (700 ml) and the reaction was heated at reflux for 3.5 hours. The reaction was cooled, excess thionyl chloride was removed in vacuo, the residue was taken up in water (500 ml) and this aqueous solution was taken to pH 9 by addition of saturated aqueous sodium bicarbonate solution (300 ml). The aqueous phase was extracted with dichloromethane (2×400 ml), the organic solution was washed with brine (400 ml) and the solvents were removed in vacuo. Trituration of the solid residue with ethyl acetate (150 ml), followed by drying in vacuo, yielded 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (53 g, 60% yield) as a pale brown solid:
Workup
- temperaturethe reaction was heated
- temperatureat reflux for 3.5 hours
- temperatureThe reaction was cooled
- customexcess thionyl chloride was removed in vacuo
- additionthis aqueous solution was taken to pH 9 by addition of saturated aqueous sodium bicarbonate solution (300 ml)
- extractionThe aqueous phase was extracted with dichloromethane (2×400 ml)
- washthe organic solution was washed with brine (400 ml)
- customthe solvents were removed in vacuo
- customby drying in vacuo
Sources & evidence
- ORD record
- ord-857f6ced954041d29f5be79c2734c79a
- Source dataset
- uspto-grants-2007_06
- Patent number
- US07235559B1
Reaction notes
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