Potassium Carbonate → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-[2-(2-oxo-1,2-dihydro-1-pyridyl)ethoxy]quinazoline

HRID 1420923Notes

Reaction equation

HRID 1420923 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Cl[CH2:24][CH2:25][N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]1=[O:32].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:24][CH2:25][N:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]4=[O:32])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 127048731-(2-Chloroethyl)pyridin-2(1H)-oneHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 226250364-(4-Chloro-2-fluoroanilino)-6-methoxy-7-[2-(2-oxo-1,2-dihydro-1-pyridyl)ethoxy]quinazolineYield 12.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (300 mg, 0.94 mmol), (prepared as described for the starting material in Example 15), 1-(2-chloroethyl)-1,2-dihydro-2-pyridone (1 75 mg, 1.11 mmol), (J. Am. Chem. Soc. 1951, 73, 3635), and potassium carbonate (260 mg, 1.9 mmol) in DMF (30 ml) was heated at 80° C. for 3 hours, allowed to cool to ambient temperature and stirred for a further 18 hours. The mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, dried (MgSO4) and the solvent removed by evaporation. The residue ,as purified by column chromatography eluting with methylene chloride/methanoUtriethylamine mixtures (100/0/0 increasing to 70/30/0.5) to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-[2-(2-oxo-1,2-dihydro-1-pyridyl)ethoxy]quinazoline (50 mg, 12%).

Workup

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with water
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue ,as purified by column chromatography
  8. washeluting with methylene chloride/methanoUtriethylamine mixtures (100/0/0 increasing to 70/30/0.5)

Sources & evidence

ORD record
ord-67cdef5e62454c308f8a726028570572
Source dataset
uspto-grants-2000_06
Patent number
US06071921

Reaction notes

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