Dimethylformamide → 4-Chloro-6-methoxyquinazolin-7-ol
Reaction equation
CN(C)C=O.C([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14](=O)[NH:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])(=O)C.S(Cl)([Cl:25])=O>>[Cl:25][C:14]1[C:13]2[C:18](=[CH:19][C:10]([OH:9])=[C:11]([O:21][CH3:22])[CH:12]=2)[N:17]=[CH:16][N:15]=1Participants
Procedure
Dimethylformamide (0.5 ml) was added to a solution of 7-(acetoxy)-6-methoxyquinazolin-4-(3H)-one (2.0 g, 8.5 mmol) in thionyl chloride (32 ml) and the reaction mixture was heated at reflux for 1.5 hours. Upon cooling to ambient temperature, the thionyl chloride was removed in vacuo and azeotroped twice with toluene. The residue was diluted with dichloromethane (15 ml), a solution of 10% ammonia in methanol (80 ml) added and the mixture heated at 80° C. for 10 minutes. Upon cooling to ambient temperature, the solvent was evaporated to almost complete dryness, water was added and the pH adjusted to 7 with dilute hydrochloric acid. The resultant precipitate was collected by filtration and dried in vacuo at 35° C. for 18 hours to yield 4-chloro-7-hydroxy-6-methoxyquinazoline (1.65 g, 92% yield):
Workup
- temperaturethe reaction mixture was heated
- temperatureat reflux for 1.5 hours
- customthe thionyl chloride was removed in vacuo
- customazeotroped twice with toluene
- additionThe residue was diluted with dichloromethane (15 ml)
- additiona solution of 10% ammonia in methanol (80 ml) added
- temperaturethe mixture heated at 80° C. for 10 minutes
- temperatureUpon cooling to ambient temperature
- customthe solvent was evaporated to almost complete dryness, water
- additionwas added
- filtrationThe resultant precipitate was collected by filtration
- customdried in vacuo at 35° C. for 18 hours
Sources & evidence
- ORD record
- ord-ea2800421d8c4f5b9053e206232df509
- Source dataset
- uspto-grants-2010_04
- Patent number
- US07691867B2
Reaction notes
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