Potassium Carbonate → 4-(4-Chloro2-fluoroanilino)-7-(3-ethoxycarbonylpropoxy)6-methoxyquinazoline

HRID 1838572Notes

Reaction equation

HRID 1838572 reaction equation
Cl[CH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[Cl:10][C:11]1[CH:30]=[CH:29][C:14]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:13]([F:31])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(Cl)Cl>[Cl:10][C:11]1[CH:30]=[CH:29][C:14]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:13]([F:31])[CH:12]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 18474Ethyl 4-chlorobutyrateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 224783014-(4-Chloro2-fluoroanilino)-7-(3-ethoxycarbonylpropoxy)6-methoxyquinazolineYield 53%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
105 °C

Procedure

Ethyl 4-chlorobutyrate (0.154 ml, 1.1 mmol) was added to a mixture of 4-(4chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (319.5 mg, 1 mmol), (prepared as described for the starting material in Example 2), and anhydrous potassium carbonate (690 mg, 5 mmol) in DMF (10 ml). The mixture was stirred and heated at 105° C. for 4 hours then allowed to cool. The mixture was diluted with methylene chloride and the insolubles were removed by filtration. The solvent was removed from the filtrate by evaporation and the residue was purified by column chromatography eluting with methylene chloride/methanol/aqueous ammonia (100/8/1). The purified product was triturated with ether collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-7-(3-ethoxycarbonylpropoxy)-6-methoxyquinazoline (230 mg, 53%).

Workup

  1. custom(prepared
  2. temperatureto cool
  3. customthe insolubles were removed by filtration
  4. customThe solvent was removed from the filtrate by evaporation
  5. customthe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol/aqueous ammonia (100/8/1)
  7. customThe purified product was triturated with ether
  8. filtrationcollected by filtration
  9. customdried

Sources & evidence

ORD record
ord-fe5edd2c7e624cdd94aef222bc0d1df2
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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