Triphosgene → N-(2,4-Difluorobenzyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}urea

HRID 1008345Notes

Reaction equation

HRID 1008345 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([F:23])[CH:17]=1.ClC(Cl)(O[C:28](=[O:34])OC(Cl)(Cl)Cl)Cl.[F:36][C:37]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:38]=1[CH2:39][NH2:40].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.ClCCl.C(N(CC)CC)C>[F:36][C:37]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:38]=1[CH2:39][NH:40][C:28]([NH:20][C:19]1[CH:21]=[CH:22][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[CH:17][C:18]=1[F:23])=[O:34]

Participants

8

Reactant 4

HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 27332442,4-DifluorobenzylamineHCID 113014704-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline

Product 1

HCID 15515589N-(2,4-Difluorobenzyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}ureaYield 80%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (100 mg) was dissolved in toluene (5.0 ml) and triethylamine (1.0 ml) with heating. A solution of triphosgene (103 mg) in dichloromethane (1.0 ml) was then added to the solution, and the mixture was heated under reflux for 3 min. Next, 2,4-difluorobenzylamine (54 mg) was added thereto, and the mixture was heated under reflux for additional 5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, followed by extraction with chloroform. The chloroform 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/acetone (2/1) to give 123 mg (yield 80%) of the title compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3 min
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for additional 5 hr
  5. extractionfollowed by extraction with chloroform
  6. dry with materialThe chloroform layer was dried over anhydrous sodium sulfate
  7. customThe solvent was removed by distillation under the reduced pressure
  8. customThe residue was purified by chromatography on silica gel by development with chloroform/acetone (2/1)

Sources & evidence

ORD record
ord-f7947f11ae1a406e900ec1d38cf4fc00
Source dataset
uspto-grants-2004_09
Patent number
US06797823B1

Reaction notes

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