Thionyl Chloride → 4-Chloro-6-methoxyquinazolin-7-ol
Reaction equation
C([O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9](=O)[NH:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:16][CH3:17])(=O)C.S(Cl)([Cl:20])=O>CN(C)C=O>[Cl:20][C:9]1[C:8]2[C:13](=[CH:14][C:5]([OH:4])=[C:6]([O:16][CH3:17])[CH:7]=2)[N:12]=[CH:11][N:10]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
7-Acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one (1 g, 4.3 mmol) was suspended in thionyl chloride (10.5 ml). One drop of dimethylformamide was added and the reaction was heated to 80° C. for two hours, during which time the solid dissolved. The reaction mixture was cooled and the thionyl chloride was removed in vacuo. The residue was azeotroped with toluene before being suspended in methylene chloride. A solution of 10% ammonia in methanol (40 ml) was added and the reaction mixture was heated to 80° C. for 15 minutes. After cooling the solvents were removed in vacuo and the residue redissolved in water (10 ml) and the pH adjusted to 7.0 with 2M hydrochloric acid. The resulting solid was filtered, washed with water and dried over phosphorus pentoxide yielding 4-chloro-7-hydroxy-6-methoxyquinazoline as a white solid (680 mg, 75%).
Workup
- dissolutiondissolved
- temperatureThe reaction mixture was cooled
- customthe thionyl chloride was removed in vacuo
- customThe residue was azeotroped with toluene
- additionA solution of 10% ammonia in methanol (40 ml) was added
- temperaturethe reaction mixture was heated to 80° C. for 15 minutes
- temperatureAfter cooling the solvents
- customwere removed in vacuo
- dissolutionthe residue redissolved in water (10 ml)
- filtrationThe resulting solid was filtered
- washwashed with water
- dry with materialdried over phosphorus pentoxide
Sources & evidence
- ORD record
- ord-53d4aeb544ea4b2daa0747f7e99241df
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08293902B2
Reaction notes
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