Potassium Carbonate → HCID 22625001, compound

HRID 279547Notes

Reaction equation

HRID 279547 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+].Cl.Cl[CH2:31][C:32]1[N:33]=[C:34]([CH3:37])[S:35][CH:36]=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][CH2:31][C:32]4[N:33]=[C:34]([CH3:37])[S:35][CH:36]=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

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27342034-(Chloromethyl)-2-methyl-1,3-thiazole--hydrogen chloride (1/1)HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22625001HCID 22625001, compoundYield 73.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (448 mg, 1.4 mmol), (prepared as described for the starting material in Example 24), and potassium carbonate (676 mg, 4.9 mmol) in DMF (10 ml) was stirred at ambient temperature for 10 minutes. 4-Chloromethyl-2-methylthiazole hydrochloride (310 mg, 1.68 mmol) was added and the mixture was heated at 70° C. for 3.5 hours. The reaction mixture was allowed to cool and was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried (MgSO4) and the solvent removed by evaporation. The solid residue was purified by column chromatography eluting with a mixture of methylene chloride/acetonitrile/methanol (50/45/5 followed by 50/40/10). The resulting purified solid was dissolved in methylene chloride/methanol and a solution of 5M hydrogen chloride in isopropanol (1 ml) was added. Partial evaporation led to the precipitation of a white solid. This solid was collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-((2-methylthiazol-4-yl)methoxy)quinazoline hydrochloride (240 mg, 35%).

Workup

  1. custom(prepared
  2. temperaturethe mixture was heated at 70° C. for 3.5 hours
  3. temperatureto cool
  4. customwas partitioned between ethyl acetate and water
  5. customThe organic layer was separated
  6. washwashed with water, brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe solid residue was purified by column chromatography
  10. washeluting with a mixture of methylene chloride/acetonitrile/methanol (50/45/5 followed by 50/40/10)
  11. customThe resulting purified solid
  12. dissolutionwas dissolved in methylene chloride/methanol
  13. additiona solution of 5M hydrogen chloride in isopropanol (1 ml) was added
  14. customPartial evaporation
  15. customled to the precipitation of a white solid
  16. filtrationThis solid was collected by filtration
  17. customdried under vacuum

Sources & evidence

ORD record
ord-4e9692cfffa6456f892cc108e2556a52
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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