Piperidine → N-(2-Chloro-4-{[6-methoxy-7-(3-piperidino-propoxy)-4-quinazolinyl]oxy}phenyl)-N'-propylurea

HRID 1008443Notes

Reaction equation

HRID 1008443 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([O:16][C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:26][CH2:27][CH2:28][CH3:29])=[O:25])=[C:19]([Cl:30])[CH:18]=3)=[N:11][CH:12]=[N:13]2)=[CH:8][C:7]=1[O:31][CH3:32].C(=O)([O-])[O-].[K+].[K+].[NH:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1>CN(C)C=O>[Cl:30][C:19]1[CH:18]=[C:17]([O:16][C:10]2[C:9]3[C:14](=[CH:15][C:6]([O:5][CH2:4][CH2:3][CH2:2][N:39]4[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]4)=[C:7]([O:31][CH3:32])[CH:8]=3)[N:13]=[CH:12][N:11]=2)[CH:22]=[CH:21][C:20]=1[NH:23][C:24]([NH:26][CH2:27][CH2:28][CH3:29])=[O:25]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 11430Potassium CarbonateHCID 22667067N-(4-{[7-(3-bromopropoxy)-6-methoxy-4-quinazolinyl]oxy}-2-chlorophenyl)-N'-propylurea

Product 1

HCID 22667084N-(2-Chloro-4-{[6-methoxy-7-(3-piperidino-propoxy)-4-quinazolinyl]oxy}phenyl)-N'-propylureaYield 50%

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. additionA saturated aqueous sodium hydrogencarbonate solution 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. customThe residue was purified by chromatography on silica gel by development with chloroform/methanol (20/1)

Sources & evidence

ORD record
ord-8001a546f1dd41838263959e553f1133
Source dataset
uspto-grants-2004_09
Patent number
US06797823B1

Reaction notes

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