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

HRID 1008412Notes

Reaction equation

HRID 1008412 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][N: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.[CH2:37]([NH2:40])[C:38]#[CH:39].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.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][N:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:28]([NH:40][CH2:37][C:38]#[CH:39])=[O:34])=[C:18]([F:23])[CH:17]=1

Participants

7

Reactant 4

HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 11205720Prop-2-ynylamine hydrochlorideHCID 218902744-((6,7-Dimethoxy-4-quinazolinyl)oxy]-2-fluoroaniline

Product 1

HCID 22667153N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-fluorophenyl}-N'-(2-propynyl)ureaYield 33.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 8471TriethylamineSolvent

Procedure

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-fluoro-aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.3 ml), and a solution of triphosgene (47 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 min. Next, propargylamine hydrochloride (29 mg) was added to the reaction solution, and the mixture was further stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was washed with chloroform to give 21 mg (yield 33%) of the title compound.

Workup

  1. stirringthe mixture was further stirred at room temperature overnight
  2. extractionthe mixture was extracted with chloroform
  3. dry with materialThe chloroform layer was dried over anhydrous sodium sulfate
  4. customThe solvent was removed by distillation under the reduced pressure
  5. washThe residue was washed with chloroform

Sources & evidence

ORD record
ord-425876e4ec444a22b26efd434973595c
Source dataset
uspto-grants-2004_09
Patent number
US06797823B1

Reaction notes

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