Dimethylformamide → 4-(4-Chloro-2-fluoroanilino)-7-(3-hydroxypropoxy)-6-methoxyquinazoline

HRID 1596253Notes

Reaction equation

HRID 1596253 reaction equation
Cl.C([O:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=3[F:32])=[N:19][CH:20]=[N:21]2)=[CH:16][C:15]=1[O:33][CH3:34])C1C=CC=CC=1.CN(C=O)C>[Pd].CO.ClC(Cl)Cl>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:18]2[C:17]3[C:22](=[CH:23][C:14]([O:13][CH2:12][CH2:11][CH2:10][OH:9])=[C:15]([O:33][CH3:34])[CH:16]=3)[N:21]=[CH:20][N:19]=2)=[C:26]([F:32])[CH:27]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 226248927-(3-Benzyloxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride

Product 1

HCID 217015564-(4-Chloro-2-fluoroanilino)-7-(3-hydroxypropoxy)-6-methoxyquinazolineYield 33%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A mixture of 7-(3-benzyloxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (180 mg, 0.4 mmol) and 5% palladium-on-charcoal catalyst (50 mg) in methanol (5 m), trichloromethane (5 ml) a nd DMF (1 ml) was stirred under hydrogen at 1 atmosphere pressure for 2 hours. The catalyst was removed by filtration through diatomaceous earth and the solvent removed by evaporation. The residue was partitioned between ethyl acetate and aqueous sodium hydrogen carbonate solution, the organic layer separated and dried (MgSO4) and the solvent removed by evaporation. The residue was recrystallised from ethyl acetate/hexane to give 4-(4-chloro-2-fluoroanilino)-7-(3-hydroxypropoxy)-6-methoxyquinazoline (48 mg, 33%).

Workup

  1. customThe catalyst was removed by filtration through diatomaceous earth
  2. customthe solvent removed by evaporation
  3. customThe residue was partitioned between ethyl acetate and aqueous sodium hydrogen carbonate solution
  4. customthe organic layer separated
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was recrystallised from ethyl acetate/hexane

Sources & evidence

ORD record
ord-764f10638f064788ae896b818ff45afb
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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