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

HRID 2182557Notes

Reaction equation

HRID 2182557 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 4chlorobutyrate (0.154 ml, 1.1 mmol) was added to a mixture of 4{4-chloro-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 110 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%). 1H NMR Spectrum: (DMSOd6) 1.18(t, 3H); 2.02(m, 2H); 2.48(hi, 2H); 3.94(s, 3H); 4.06(q, MS-ESI: 434 [MH]+

Workup

  1. custom(prepared
  2. temperatureto cool
  3. customthe insolubles were removed by 110 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-0abf8bd589744d8e836e4916f83b3616
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

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