Hexane → 7-Acetoxy4-(5-benzyloxy-2-fluoro-4-methylanilino)-6-methoxyquinazoline

HRID 634677Notes

Reaction equation

HRID 634677 reaction equation
[C:1]([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:3])[CH3:2].S(Cl)(Cl)=O.[CH2:22]([O:29][C:30]1[C:31]([CH3:38])=[CH:32][C:33]([F:37])=[C:34]([CH:36]=1)[NH2:35])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CCCCCC>CN(C=O)C.C(O)(C)C>[C:1]([O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([NH:35][C:34]3[CH:36]=[C:30]([O:29][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:31]([CH3:38])=[CH:32][C:33]=3[F:37])=[N:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:16][CH3:17])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 8058HexaneHCID 24386Thionyl ChlorideHCID 219910685-Benzyloxy-2-fluoro-4-methylanilineHCID 1356979057-Acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one

Product 1

HCID 212603127-Acetoxy4-(5-benzyloxy-2-fluoro-4-methylanilino)-6-methoxyquinazolineYield 43%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 3776IsopropanolSolvent

Procedure

A mixture of 7-acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one (1.69 g, 7.2 mmol), thionyl chloride (50 ml) and DMF (3 drops) was heated at reflux for 2 hours. The excess thionyl chloride was removed by evaporation and the residue azeotroped with toluene. The residue was partitioned between methylene chloride and saturated aqueous sodium hydrogen carbonate solution. The organic phase was separated, dried (MgSO4) and the solvent removed by evaporation. 5-Benzyloxy-2-fluoro-4-methylaniline (1.8 g, 7.8 mmol) in isopropanol (50 ml) was added to the residue and the mixture heated at reflux for 2 hours. The mixture was allowed to cool, hexane added and the precipitated product collected by filtration to give 7-acetoxy-4-(5-benzyloxy-2-fluoro-4-methylanilino)-6-methoxyquinazoline (1.34 g, 43%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. customThe excess thionyl chloride was removed by evaporation
  4. customthe residue azeotroped with toluene
  5. customThe residue was partitioned between methylene chloride and saturated aqueous sodium hydrogen carbonate solution
  6. customThe organic phase was separated
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. temperaturethe mixture heated
  10. temperatureat reflux for 2 hours
  11. temperatureto cool
  12. filtrationthe precipitated product collected by filtration

Sources & evidence

ORD record
ord-ebb58f8a97c24a4e87a477c597871eff
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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