HCID 21260325, compound → HCID 135549381, compound

HRID 634655Notes

Reaction equation

HRID 634655 reaction equation
[C:1]([O:4][C:5]1[C:6]([Cl:33])=[CH:7][C:8]([F:32])=[C:9]([CH:31]=1)[NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:23]CC3C=CC=CC=3)=[C:18]([O:21][CH3:22])[CH:19]=2)[N:14]=[CH:13][N:12]=1)(=[O:3])[CH3:2]>CO.ClC(Cl)Cl.CN(C=O)C.[Pd]>[C:1]([O:4][C:5]1[C:6]([Cl:33])=[CH:7][C:8]([F:32])=[C:9]([CH:31]=1)[NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([OH:23])=[C:18]([O:21][CH3:22])[CH:19]=2)[N:14]=[CH:13][N:12]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 1

HCID 21260325HCID 21260325, compound

Product 1

HCID 135549381HCID 135549381, compoundYield 83.3%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(5-acetoxy-4-chloro-2-fluoroanilino)-7-benzyloxy-6-methoxyquinazoline (250 mg, 0.54 mmol) in methanol (5 ml), trichloromethane (5 ml) and DMF (1 ml) was stirred under hydrogen at 1 atmosphere with 5% palladium-on-charcoal catalyst (100 mg) for 4 hours. The catalyst was removed by filtration through diatomaceous earth and the solvent removed by evaporation. The residue was dissolved in ethyl acetate, washed with water and brine, and dried (MgSO4). Most of the solvent was removed by evaporation, the mixture was cooled and hexane added to obtain solid product which was collected by filtration, washed with hexane/ethyl acetate and dried to give 4-(5-acetoxy-4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (170 mg, 45%).

Workup

  1. customThe catalyst was removed by filtration through diatomaceous earth
  2. customthe solvent removed by evaporation
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. customMost of the solvent was removed by evaporation
  7. temperaturethe mixture was cooled
  8. additionhexane added
  9. customto obtain solid product which
  10. filtrationwas collected by filtration
  11. washwashed with hexane/ethyl acetate
  12. customdried

Sources & evidence

ORD record
ord-796548ede6634eebbcee85dbc2b31d29
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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