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

HRID 1354044Notes

Reaction equation

HRID 1354044 reaction equation
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]

Participants

6

Reactant 4

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

Product 1

HCID 1355250806-Methoxy-7-(3-(pyrrolidin-1-YL)propoxy)quinazolin-4-OLYield 83.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

After repetition of the previous reaction, a mixture of 2-amino-5-methoxy-4-(3-pyrrolidin-1-ylpropoxy)benzamid 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 pH8 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, 2H), 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).

Workup

  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
  7. dissolutionThe residue was 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

Sources & evidence

ORD record
ord-daccc2f4d9f6451a9a574cda929bbb50
Source dataset
uspto-grants-2007_05
Patent number
US07223756B2

Reaction notes

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