Potassium Carbonate → HCID 22625040, compound

HRID 279606Notes

Reaction equation

HRID 279606 reaction equation
S(Cl)(Cl)=O.[OH:5][CH2:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([O:13][CH3:14])[CH:8]=1.[Cl:15][C:16]1[CH:35]=[CH:34][C:19]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](O)=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)=[C:18]([F:36])[CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CN(C=O)C.O>[Cl:15][C:16]1[CH:35]=[CH:34][C:19]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:5][CH2:6][C:7]4[CH:12]=[CH:11][N:10]=[C:9]([O:13][CH3:14])[CH:8]=4)=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)=[C:18]([F:36])[CH:17]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 14462410(2-Methoxypyridin-4-yl)methanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22625040HCID 22625040, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

Thionyl chloride (0.6 ml) was added to a solution of 4-hydroxymethyl-2-methoxypyridine (0.59 g, 4.2 mmol) in toluene (10 ml) and the mixture stirred at ambient temperature for 1.5 hours. The volatiles were removed by evaporation and the residue was azeotroped with toluene and dried under vacuum to give crude 4-chloromethyl-2-methoxypyridine hydrochloride (0.50 g, 2.6 mmol) which was used directly. This product was then added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (420 mg, 1.3 mmol), (prepared as described for the starting material in Example 24), and potassium carbonate (1.0 g 7 mmol) in DMF (8 ml) and the resulting mixture was heated at 75° C. for 2 hours. The mixture was allowed to cool, diluted with water and the precipitated solid collected by filtration, washed with water and dried to give 4-(4-chloro-2-fluoroanilino)-7-((2-methoxy-4-pyridyl)methoxy)-6-methoxyquinazoline (140 mg, 25%).

Workup

  1. customThe volatiles were removed by evaporation
  2. customthe residue was azeotroped with toluene
  3. customdried under vacuum
  4. customto give crude 4-chloromethyl-2-methoxypyridine hydrochloride (0.50 g, 2.6 mmol) which
  5. custom(prepared
  6. temperaturethe resulting mixture was heated at 75° C. for 2 hours
  7. temperatureto cool
  8. filtrationthe precipitated solid collected by filtration
  9. washwashed with water
  10. customdried

Sources & evidence

ORD record
ord-2e8b85151c2e488a9601d78ebcca5b8f
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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