Dimethylformamide → 4-Chloro-6,7-dimethoxyquinazoline

HRID 2233251Notes

Reaction equation

HRID 2233251 reaction equation
CN(C)C=O.[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH2:19]C1C=CC=CC=1)[N:14]=[CH:13][NH:12][C:11]2=O.S(Cl)([Cl:29])=O>>[Cl:29][C:11]1[C:10]2[C:15](=[CH:16][C:17]([O:18][CH3:19])=[C:8]([O:7][CH3:6])[CH:9]=2)[N:14]=[CH:13][N:12]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 1354047187-Benzyloxy-6-methoxy-3H-quinazolin-4-one

Product 1

HCID 27693644-Chloro-6,7-dimethoxyquinazolineYield 90%

Procedure

A mixture of 2-amino-4-benzyloxy-5-methoxybenzamide (10 g, 0.04 mol—prepared according to J. Med. Chem. 1977, 20, 146-149), and Gold's reagent (7.4 g, 0.05 mol) in dioxane (100 ml) was stirred and heated at reflux for 24 hours. Sodium acetate (3.02 g, 0.037 mol) and acetic acid (1.65 ml, 0.029 mol) were added to the reaction mixture and it was heated for a further 3 hours. The volatiles were removed by evaporation, water was added to the residue, the solid was collected by filtration, washed with water and dried. Recrystallisation from acetic acid yielded 7-benzyloxy-6-methoxy-3,4-dihydroquinazolin-4-one (8.7 g, 84% yield) as a white solid. b) Dimethylformamide (0.2 ml) was added dropwise to a solution of 6-methoxy-7-benzyloxy-3,4-dihydroquinazolin-4-one (5.00 g, 17.9 mmol) in thionyl chloride (100 ml) and the reaction was heated at reflux for 1 hour. The reaction was cooled, excess thionyl chloride was removed in vacuo and the residue was azeotroped with toluene (3×50 ml) to remove the last of the thionyl chloride. The residue was taken up in dichloromethane (550 ml), the solution was washed with saturated aqueous sodium hydrogen carbonate solution (100 ml) and water (100 ml) and the organic phase was dried over magnesium sulphate. Solvent evaporation in vacuo yielded 4-chloro-6,7-dimethoxyquinazoline (4.80 g, 90% yield) as a pale brown solid:

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 1 hour
  3. temperatureThe reaction was cooled
  4. customexcess thionyl chloride was removed in vacuo
  5. customthe residue was azeotroped with toluene (3×50 ml)
  6. customto remove the last of the thionyl chloride
  7. washthe solution was washed with saturated aqueous sodium hydrogen carbonate solution (100 ml) and water (100 ml)
  8. dry with materialthe organic phase was dried over magnesium sulphate
  9. customSolvent evaporation in vacuo

Sources & evidence

ORD record
ord-b9439fec5d134bd1ac73356c63b6ed95
Source dataset
uspto-grants-2010_05
Patent number
US07709479B1

Reaction notes

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