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

HRID 453998Notes

Reaction equation

HRID 453998 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-cec2d5c0f4d64ad78f54393adc9aa63a
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…