1,3-Dibromopropane → N-(4-{[7-(3-bromopropoxy)-6-methoxy-4-quinazolinyl]oxy}-2-chlorophenyl)-N'-propylurea

HRID 1008442Notes

Reaction equation

HRID 1008442 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][CH2:38]Br>CN(C)C=O>[Br:35][CH2:36][CH2:37][CH2:38][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 80011,3-DibromopropaneHCID 11430Potassium CarbonateHCID 135674214N-(2-Chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea

Product 1

HCID 22667067N-(4-{[7-(3-bromopropoxy)-6-methoxy-4-quinazolinyl]oxy}-2-chlorophenyl)-N'-propylureaYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-{2-Chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N′-propylurea (500 mg), potassium carbonate (857 mg), and 1,3-dibromopropane (0.5 ml) were dissolved in N,N-dimethylformamide (5 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/2-propanol (4/1). 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 451 mg (yield 71%) of N-(4-{[7-(3-bromopropoxy)-6-methoxy-4-quinazolinyl]oxy}-2-chlorophenyl}-N′-propyl-urea. N-(4-{[7-(3-Bromopropoxy)-6-methoxy-4-quinazolinyl]oxy}-2-chlorophenyl}-N′-propylurea (70 mg), potassium carbonate (54 mg), and piperidine (39 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. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform/methanol (20/1) to give 35 mg (yield 50%) 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/2-propanol (4/1)
  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-1198a7f5f4bf4897961dd729f90ba2c8
Source dataset
uspto-grants-2004_09
Patent number
US06797823B1

Reaction notes

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