Thionyl Chloride → 4-Chloro-6,7-dimethoxyquinazoline

HRID 1791531Notes

Reaction equation

HRID 1791531 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][NH:7][C:6]2=O.S(Cl)([Cl:18])=O>CN(C=O)C>[Cl:18][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 1354950166,7-Dimethoxy-3H-quinazolin-4-one

Product 1

HCID 27693644-Chloro-6,7-dimethoxyquinazoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

6,7-Dimethoxy-3,4-dihydroquinazolin-4-one (290 mg, 1.4 mmol) was suspended in thionyl chloride (5 ml) and DMF (2 drops) and heated at reflux for 2 hours. The thionyl chloride was evaporated under vacuum and the residue azeotroped with toluene three times to give 4-chloro-6,7-dimethoxyquinazoline. A mixture of the crude 4-chloro-6,7-dimethoxyquinazoline, potassium carbonate (970 mg, 7 mmol) and 7-hydroxyquinoline (235 mg, 1.62 mmol) in DMF (10 ml) was stirred at 100° C. for 5 hours and allowed to cool to ambient temperature overnight. The reaction mixture was treated with 1M aqueous sodium hydroxide solution and stirred at ambient temperature for a few minutes. The reaction mixture was extracted with ethyl acetate (×4) and the organic extracts washed with water and brine. The organic extracts were dried (MgSO4), filtered and the solvent removed under vacuum. The residue was triturated with ethyl acetate and then recrystallised from hot ethyl acetate to give 6,7-dimethoxy-4-(quinolin-7-yloxy)quinazoline (110 mg, 24%) as a white solid.

Workup

  1. temperatureat reflux for 2 hours
  2. customThe thionyl chloride was evaporated under vacuum
  3. customthe residue azeotroped with toluene three times

Sources & evidence

ORD record
ord-0c43765f9a3f4cde8df5f300566eb048
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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