7-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)6-methoxyquinazoline → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-methyl-4H-1,2,4-triazol-3-ylthio)ethoxy)-quinazoline hydrochloride

HRID 279584

Reaktionsgleichung

Reaktionsgleichung von HRID 279584
Br[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[F:23])=[N:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:24][CH3:25].[CH3:26][N:27]1[CH:31]=[N:30][N:29]=[C:28]1[SH:32].CC(C)([O-])C.[K+]>CN(C=O)C>[ClH:22].[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][C:9]2[C:8]3[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][S:32][C:28]4[N:27]([CH3:26])[CH:31]=[N:30][N:29]=4)=[C:6]([O:24][CH3:25])[CH:7]=3)[N:12]=[CH:11][N:10]=2)=[C:17]([F:23])[CH:18]=1

Komponenten

5

Edukt 3

HCID 187534227-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)6-methoxyquinazolineHCID 23665647Potassium tert-butoxideHCID 178481306HCID 178481306, Verbindung

Produkt 1

HCID 226249754-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-methyl-4H-1,2,4-triazol-3-ylthio)ethoxy)-quinazoline hydrochlorideAusbeute 157,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

7-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (98 mg, 0.23 mmol) was added to a solution of 4-methyl-4H-1,2,4-triazole-3-thiol (40 mg, 0.34 mmol) and potassium-t-butoxide (36 mg, 0.32 mmol) in DMF (1 ml) and the mixture heated at 40° C. for 30 minutes. The reaction mixture was allowed to cool and was partitioned between ammonium chloride and ethyl acetate. The organic layer was separated, washed with water and brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with a gradient of methylene chloride/methanol (95/50 to 80/20). The purified solid product was triturated with ether and collected by filtration. The solid was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation and the residue was crystallised from methylene chloride and ether. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-methyl-4H-1,2,4-triazol-3-ylthio)ethoxy)-quinazoline hydrochloride (90 mg, 79%).

Aufarbeitung

  1. temperatureto cool
  2. customwas partitioned between ammonium chloride and ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with a gradient of methylene chloride/methanol (95/50 to 80/20)
  9. customThe purified solid product was triturated with ether
  10. filtrationcollected by filtration
  11. dissolutionThe solid was dissolved in methylene chloride/methanol
  12. addition3M ethereal hydrogen chloride (0.5 ml) was added
  13. customThe volatiles were removed by evaporation
  14. customthe residue was crystallised from methylene chloride and ether
  15. filtrationThe solid was collected by filtration
  16. washwashed with ether
  17. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-6fa8718e601e4ad883b4e64fe1f51ef3
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06362336B1

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