1,4-Dioxane → 6-Methoxy-7-(3-(pyrrolidin-1-YL)propoxy)quinazolin-4-OL

HRID 495382Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 495382
Cl.[NH2:2][C:3]1[CH:11]=[C:10]([O:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:9]([O:21][CH3:22])=[CH:8][C:4]=1[C:5]([NH2:7])=[O:6].[CH3:23]N(C=NC=[N+](C)C)C.[Cl-].O1CCOCC1.C([O-])(=O)C.[Na+]>C(O)(=O)C>[CH3:22][O:21][C:9]1[CH:8]=[C:4]2[C:3](=[CH:11][C:10]=1[O:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[N:2]=[CH:23][NH:7][C:5]2=[O:6]

Komponenten

6

Edukt 4

HCID 312751,4-DioxaneHCID 517045Sodium AcetateHCID 11008255Gold's ReagentHCID 218748202-Amino-5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzamide hydrochloride

Produkt 1

HCID 1355250806-Methoxy-7-(3-(pyrrolidin-1-YL)propoxy)quinazolin-4-OLAusbeute 83,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Versuchsvorschrift

After repetition of the previous reaction, a mixture of 2-amino-5-methoxy-4-(3-pyrrolidin-1-ylpropoxy)benzamide hydrochloride (5.92 g), Gold's reagent (3.5 g) and dioxane (50 ml) was heated to reflux for 5 hours. Acetic acid (0.7 ml) and sodium acetate (1.33 g) were added and the reaction mixture was heated to reflux for a further 5 hours. The mixture was allowed to cool to ambient temperature and evaporated The residue was dissolved in water, adjusted to pH 8 with 2N aqueous sodium hydroxide solution and purified on a Diaion HP20SS resin column eluting with methanol (gradient 0-50%) in water. The fractions containing product were concentrated by evaporation and then freeze dried to give 6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)-3,4-dihydroquinazolin-4-one (4.55 g); NMR Spectrum: (DMSOd6 and CF3CO2D) 1.9 (m, 2H), 2.0-2.1 (m, 2H), 2.2-2.3 (m, 2H), 3.05 (m, 2H), 3.34 (t, 2M), 3.6-3.7 (br s, 2H), 3.94 (s, 3H), 4.27 (t, 2H), 7.31 (s, 1H), 7.55 (s, 1H), 9.02 (s, 1H).

Aufarbeitung

  1. customAfter repetition of the previous reaction
  2. temperaturewas heated
  3. temperatureto reflux for 5 hours
  4. temperaturethe reaction mixture was heated
  5. temperatureto reflux for a further 5 hours
  6. customevaporated The residue
  7. dissolutionwas dissolved in water
  8. custompurified on a Diaion HP20SS resin column
  9. washeluting with methanol (gradient 0-50%) in water
  10. additionThe fractions containing product
  11. concentrationwere concentrated by evaporation
  12. customfreeze dried

Quellen und Nachweise

ORD-Eintrag
ord-067a9154e6924477ade7ef2d0c9f6a11
Quelldatensatz
uspto-grants-2005_09
Patentnummer
US06939866B2

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