Thionyl Chloride → 4-Chloro-6-methoxyquinazolin-7-ol

HRID 916393Notes

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]=1

Participants

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 ethanol (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 ethanol (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-9b8ea1f6a7c346fcbc6b3ada8ab5dc04
Source dataset: uspto-grants-2007_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07268230B2

Reaction notes

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