1,2-Dibromoethane → N-(4-{[7-(2-bromoethoxy)-6-methoxy-4-quinazolinyl]-oxy}-2-chlorophenyl)-N'-propylurea

HRID 1008433Notes

Reaction equation

HRID 1008433 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([OH:21])=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:4][C:3]=1[NH:22][C:23]([NH:25][CH2:26][CH2:27][CH3:28])=[O:24].C(=O)([O-])[O-].[K+].[K+].[Br:35][CH2:36][CH2:37]Br>CN(C)C=O>[Br:35][CH2:36][CH2:37][O:21][C:15]1[CH:14]=[C:13]2[C:18]([C:9]([O:8][C:6]3[CH:5]=[CH:4][C:3]([NH:22][C:23]([NH:25][CH2:26][CH2:27][CH3:28])=[O:24])=[C:2]([Cl:1])[CH:7]=3)=[N:10][CH:11]=[N:12]2)=[CH:17][C:16]=1[O:19][CH3:20]

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 11430Potassium CarbonateHCID 135674214N-(2-Chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea

Product 1

HCID 22667126N-(4-{[7-(2-bromoethoxy)-6-methoxy-4-quinazolinyl]-oxy}-2-chlorophenyl)-N'-propylureaYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-{2-Chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N′-propylurea (72 mg), potassium carbonate (30 mg), and 1,2-dibromoethane (62 μl) were dissolved in N,N-dimethylformamide (4 ml), and the solution was stirred at room temperature for 3 hr. The solvent was removed by distillation under the reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was washed with ether to give 40 mg (yield 45%) of N-(4-{[7-(2-bromoethoxy)-6-methoxy-4-quinazolinyl ]-oxy}-2-chlorophenyl)-N′-propylurea as an intermediate. The intermediate (45 mg), potassium carbonate (30 mg), and morpholine (80 μl) were dissolved in N,N-dimethylformamide (2 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under the reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform/methanol to give 42 mg (yield 56%) of the title compound.

Workup

  1. customThe solvent was removed by distillation under the reduced pressure
  2. additionWater was added to the residue
  3. extractionthe mixture was extracted with chloroform
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customThe solvent was removed by distillation under the reduced pressure
  6. washThe residue was washed with ether

Sources & evidence

ORD record
ord-f1014ae7d4ea4eab934e9cc5127432f3
Source dataset
uspto-grants-2004_09
Patent number
US06797823B1

Reaction notes

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