Potassium Iodide → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-((pyrimidin-4-yl)methoxy)quinazoline hydrochloride

HRID 1420959Notes

Reaction equation

HRID 1420959 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl[CH2:32][C:33]1[CH:38]=[CH:37][N:36]=[CH:35][N:34]=1>CN(C=O)C>[ClH:1].[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:32][C:33]4[CH:38]=[CH:37][N:36]=[CH:35][N:34]=4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 131235534-(Chloromethyl)pyrimidineHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 226249654-(4-Chloro-2-fluoroanilino)-6-methoxy-7-((pyrimidin-4-yl)methoxy)quinazoline hydrochlorideYield 76.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (319.5 mg, 1 mmol), (prepared as described for the starting material in Example 24), potassium carbonate (414 mg, 3 mmol), potassium iodide (16 mg, 0.1 mmol) and 4-chloromethylpyrimidine (257 mg, 2 mmol) in DMF (20 ml) was heated at 80° C. for 2 hours. The solvent was removed by evaporation and the residue was triturated with water. The solid was collected by filtration and dried under vaccum. The solid was purified by column chromatography eluting with methylene chloride/methanol (95/5). The purified white solid was suspended in methanol (25 ml) and a solution of 7.5M hydrogen chloride in methanol (20 ml) was added. The resulting solid product was collected by filtration, washed with methanol and then pentane and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-((pyrimidin-4-yl)methoxy)quinazoline hydrochloride (172 mg, 42%).

Workup

  1. custom(prepared
  2. customThe solvent was removed by evaporation
  3. customthe residue was triturated with water
  4. filtrationThe solid was collected by filtration
  5. customdried under vaccum
  6. customThe solid was purified by column chromatography
  7. washeluting with methylene chloride/methanol (95/5)
  8. additiona solution of 7.5M hydrogen chloride in methanol (20 ml) was added
  9. filtrationThe resulting solid product was collected by filtration
  10. washwashed with methanol
  11. dry with materialpentane and dried under vacuum

Sources & evidence

ORD record
ord-0c519319bd08439db59acbeb45b9f4fa
Source dataset
uspto-grants-2000_06
Patent number
US06071921

Reaction notes

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