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

HRID 723498노트

반응식

HRID 723498 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 176Acetic Acid용매

실험 절차

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 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).

후처리

  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

출처 및 근거

ORD 기록
ord-b80e962a0fdc4df18f1f6426f5321f1e
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07141577B2

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