Diethylamine → N'-[2-Chloro-4-({6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]-4-quinazolinyl}oxy)phenyl]-N,N-diethylurea

HRID 1375881Notes

Reaction equation

HRID 1375881 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](=[O:29])[N:24]([CH2:27][CH3:28])[CH2:25][CH3:26].C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH2:47][CH2:48][N:49]2[CH:53]=[CH:52][N:51]=[N:50]2)(=O)=O)=CC=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.C(NCC)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(Cl)(Cl)Cl.C(N(CC)CC)C.O>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:47][CH2:48][N:49]4[CH:53]=[CH:52][N:51]=[N:50]4)=[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](=[O:29])[N:24]([CH2:27][CH3:28])[CH2:25][CH3:26]

Participants

11

Reactant 6

HCID 8021DiethylamineHCID 11430Potassium CarbonateHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 226671112-(1H-1,2,3-triazol-1-yl)ethyl 4-methyl-1-benzenesulfonateHCID 135674217N'-{2-chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N,N-diethylurea

Product 1

HCID 22667201N'-[2-Chloro-4-({6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]-4-quinazolinyl}oxy)phenyl]-N,N-diethylureaYield 29%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

A starting compound (N′-{2-chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N,N-diethylurea, 83 mg), potassium carbonate (138 mg), and 2-(1H-1,2,3-triazol-1-yl)ethyl 4-methyl-1-benzenesulfonate (59 mg) were dissolved in N,N-dimethylformamide (1 ml), and the solution was stirred at 80° C. for 18 hr. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). 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 an intermediate. Triphosgene (90 mg) was added to a solution of the intermediate and triethylamine (0.027 ml) in chloroform (1 ml) at 0° C., and the mixture was stirred for 30 min. The reaction mixture was cooled to 0° C., and diethylamine (0.044 ml) was then added dropwise to the cooled reaction mixture. The temperature of the mixture was raised to room temperature over a period of 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, followed by extraction with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by HPLC to give 30 mg (yield 29%) of the title compound.

Workup

  1. extractionthe mixture was extracted with chloroform-propanol (3/1)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. customThe solvent was removed by distillation under the reduced pressure
  4. washThe residue was washed with ether
  5. customto give an intermediate
  6. stirringthe mixture was stirred for 30 min
  7. temperatureThe reaction mixture was cooled to 0° C.
  8. temperatureThe temperature of the mixture was raised to room temperature over a period of 2 hr
  9. extractionfollowed by extraction with chloroform-propanol (3/1)
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. customThe solvent was removed by distillation under the reduced pressure
  12. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-1b3846cec726457eba2d4fda923e6c36
Source dataset
uspto-grants-2007_01
Patent number
US07169789B2

Reaction notes

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