Dimethylformamide → 4-(2,4-Difluoro-5-hydroxyanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride

HRID 634672Notes

Reaction equation

HRID 634672 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][O:16][CH3:17])[N:9]=[CH:8][NH:7][C:6]2=O.CN(C=O)C.[F:24][C:25]1[CH:31]=[C:30]([F:32])[C:29]([OH:33])=[CH:28][C:26]=1[NH2:27].S(Cl)([Cl:36])=O>>[ClH:36].[F:24][C:25]1[CH:31]=[C:30]([F:32])[C:29]([OH:33])=[CH:28][C:26]=1[NH:27][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 27829995-Amino-2,4-difluorophenolHCID 135407708HCID 135407708, compound

Product 1

HCID 212602784-(2,4-Difluoro-5-hydroxyanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochlorideYield 28%

Procedure

6-Methoxy-7-(2-methoxyethoxy)-3,4-dihydroquinazolin-4-one (200 mg, 0.8 mmol), (prepared as described for the starting material in Example 9), and DMF (0.1 ml) in thionyl chloride (20 ml) were heated at reflux for 2 hours. Excess thionyl chloride was removed by evaporation and the residue azeotroped with toluene. The residue was dissolved in isopropranol (15 ml), 2,4-difluoro-5-hydroxyaniline (128 mg, 0.88 mmol), (prepared as described for the starting material in Example 11), added, and the mixture heated at reflux for 2 hours. The reaction mixture was then allowed to cool, the precipitated product collected by filtration, washed with isopropanol and dried to give 4-(2,4-difluoro-5-hydroxyanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride (83 mg, 28%).

Workup

  1. temperaturewere heated
  2. temperatureat reflux for 2 hours
  3. customExcess thionyl chloride was removed by evaporation
  4. customthe residue azeotroped with toluene
  5. custom(prepared
  6. additionadded
  7. temperaturethe mixture heated
  8. temperatureat reflux for 2 hours
  9. temperatureto cool
  10. filtrationthe precipitated product collected by filtration
  11. washwashed with isopropanol
  12. customdried

Sources & evidence

ORD record
ord-078829b1cb55434a86c29252860235b3
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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