Potassium Iodide → HCID 22625069, compound

HRID 1384575Notes

Reaction equation

HRID 1384575 reaction equation
Cl.[Cl:2][CH2:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1.[Cl:10][C:11]1[CH:30]=[CH:29][C:14]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:13]([F:31])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C>[ClH:2].[Cl:10][C:11]1[CH:30]=[CH:29][C:14]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:3][C:4]4[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:13]([F:31])[CH:12]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22625069HCID 22625069, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

3-(Chloromethyl)pyridine hydrochloride (328 mg, 2 mmol) was added to 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 (442 mg, 3.2 mmol) and potassium iodide (33 mg, 0.2 mmol) in DMF (25 ml) at ambient temperature and the reaction mixture then heated at 80° C. for 2.5 hours. The mixture was allowed to cool and the volatiles were removed by evaporation. The residue was dissolved in a mixture of ethyl acetate (19 ml) and methanol (1 ml) and the insolubles removed by filtration. The solvent was removed from the filtrate by evaporation and the residue was purified by column chromatography eluting with methylene chloride/acetonitrile/methanol (50/45/5). The purified product was dissolved in hot methylene chloride and saturated ethereal hydrogen chloride was added. The mixture was concentrated to half volume by evaporation, the resulting precipitate was collected by filtration and dried under vacuum at 70° C. to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-((3-pyridyl)methoxy)quinazoline hydrochloride(103 mg, 25%). m.p. 216-221° C. 1H NMR Spectrum: (DMSOd6) 4.03(s, 3H); 5.48(s, 2H); 7.47(d, 1H); 7.54(s, 1H); 7.65(t, 1H); 7.7-7.8(m, 2H); 8.25(d, 1H); 8.35(s, 1H); 8.75(d, 1H); 8.84(s, 1H); 8.90(s, 1H); 11.65(br s, 1H) MS-ESI: 411 [MH]+

Workup

  1. custom(prepared
  2. customat ambient temperature
  3. temperatureto cool
  4. customthe volatiles were removed by evaporation
  5. dissolutionThe residue was dissolved in a mixture of ethyl acetate (19 ml) and methanol (1 ml)
  6. customthe insolubles removed by filtration
  7. customThe solvent was removed from the filtrate by evaporation
  8. customthe residue was purified by column chromatography
  9. washeluting with methylene chloride/acetonitrile/methanol (50/45/5)
  10. dissolutionThe purified product was dissolved in hot methylene chloride
  11. additionsaturated ethereal hydrogen chloride was added
  12. concentrationThe mixture was concentrated to half volume by evaporation
  13. filtrationthe resulting precipitate was collected by filtration
  14. customdried under vacuum at 70° C.

Sources & evidence

ORD record
ord-44d33c94858a41e8b0a04b6cbf6ce210
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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