Potassium Carbonate → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-((2-methyl-4-pyridyl)methoxy)quinazoline

HRID 279609Notes

Reaction equation

HRID 279609 reaction equation
S(Cl)(Cl)=O.[OH:5][CH2:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH3:13])[CH:8]=1.[Cl:14][C:15]1[CH:34]=[CH:33][C:18]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](O)=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)=[C:17]([F:35])[CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CN(C=O)C.O>[Cl:14][C:15]1[CH:34]=[CH:33][C:18]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:5][CH2:6][C:7]4[CH:12]=[CH:11][N:10]=[C:9]([CH3:13])[CH:8]=4)=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)=[C:17]([F:35])[CH:16]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 9942144(2-Methylpyridin-4-yl)methanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 226250564-(4-Chloro-2-fluoroanilino)-6-methoxy-7-((2-methyl-4-pyridyl)methoxy)quinazolineYield 43%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

Thionyl chloride (0.3 ml) was added to a solution of 4-hydroxymethyl-2-methylpyridine (240 mg, 1.9 mmol) in toluene (10 ml) and the mixture stirred at ambient temperature for 2 hours. The volatiles were removed by evaporation, the residue azeotroped with toluene and dried under vacuum to give crude 4-chloromethyl-2-methylpyridine hydrochloride which was used directly. This product was then added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (510 mg, 1.6 mmol), (prepared as described for the starting material in Example 24), and potassium carbonate (1.4 g 10 mmol) in DMF (8 ml) for 90 hours. The mixture was diluted with water and the precipitated solid collected by filtration, washed with water and dried to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-((2-methyl-4-pyridyl)methoxy)quinazoline (290 mg, 43%), a sample was recrystallised from ethyl acetate/hexane.

Workup

  1. customThe volatiles were removed by evaporation
  2. customthe residue azeotroped with toluene
  3. customdried under vacuum
  4. customto give crude 4-chloromethyl-2-methylpyridine hydrochloride which
  5. custom(prepared
  6. customfor 90 hours
  7. filtrationthe precipitated solid collected by filtration
  8. washwashed with water
  9. customdried

Sources & evidence

ORD record
ord-5f6b588b2d56446782553dca44255d7f
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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