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

HRID 1008348Notes

Reaction equation

HRID 1008348 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.Cl.[F:37][CH2:38][CH2:39][CH2:40][CH2:41][NH2:42].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.ClCCl.C(N(CC)CC)C>[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]([NH:20][C:28]([NH:42][CH2:41][CH2:40][CH2:39][CH2:38][F:37])=[O:34])=[C:18]([F:23])[CH:17]=1

Participants

8

Reactant 4

HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 113014704-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroanilineHCID 226671044-Fluorobutan-1-amine hydrochloride

Product 1

HCID 69351783N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N'-(4-fluorobutyl)ureaYield 58.3%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (100 mg) was dissolved in toluene (6 ml) and triethylamine (1.0 ml) with heating, and a solution of triphosgene (104 mg) in dichloromethane (1.0 ml) was then added to the solution. The mixture was heated under reflux for 5 min. Next, 4-fluorobutylamine hydrochloride (55 mg) was added to the reaction solution, and the mixture was heated under reflux for additional 2 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 80 mg (yield 55%) of the title compound.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 5 min
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for additional 2 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-2181f2f8c7eb4a7db4345a872da07056
Source dataset
uspto-grants-2004_09
Patent number
US06797823B1

Reaction notes

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