Triethylamine → N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-(4,5-dimethyl-1,3-thiazol-2-yl)urea

HRID 2416034Notes

Reaction equation

HRID 2416034 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH2:4].C(N(CC)CC)C.ClC(Cl)(O[C:35](=[O:41])OC(Cl)(Cl)Cl)Cl.Cl.[NH2:44][C:45]1[S:46][C:47]([CH3:51])=[C:48]([CH3:50])[N:49]=1>C(Cl)(Cl)Cl.O>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH:4][C:35]([NH:44][C:45]1[S:46][C:47]([CH3:51])=[C:48]([CH3:50])[N:49]=1)=[O:41]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 162113874,5-Dimethyl-1,3-thiazol-2-amine--hydrogen chloride (1/1)HCID 218898992-Chloro-4-((6,7-dimethoxyquinazolin-4-yl)oxy)aniline

Product 1

HCID 22637155N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-(4,5-dimethyl-1,3-thiazol-2-yl)ureaYield 22.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Procedure

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (100 mg) was dissolved in chloroform (5 ml) and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (100 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 15 min. Next, 2-amino-4,5-dimethylthiazole hydrochloride (50 mg) was added thereto, and the mixture was further stirred at room temperature overnight. Distilled water was added to the reaction solution, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine and was dried over sodium sulfate. The organic layer was concentrated under the reduced pressure, and the residue was purified by HPLC using chloroform/acetone for development to give 33 mg of the title compound.

Workup

  1. stirringthe mixture was further stirred at room temperature overnight
  2. extractionthe mixture was subjected to separatory extraction with chloroform
  3. washThe organic layer was washed with saturated brine
  4. dry with materialwas dried over sodium sulfate
  5. concentrationThe organic layer was concentrated under the reduced pressure
  6. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-544b768ac68d4dc5ab8619687580835b
Source dataset
uspto-grants-2004_11
Patent number
US06821987B2

Reaction notes

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