Chloroacetone → 4-(1-Ethyl-propyl)-2-methoxy-6-methyl-pyrrolo[1,2-b]pyridazine

HRID 1432712

Reaktionsgleichung

Reaktionsgleichung von HRID 1432712
[CH2:1]([CH:3]([C:6]1[CH:11]=[C:10]([O:12][CH3:13])[N:9]=[N:8][C:7]=1NC(=O)C(C)(C)C)[CH2:4][CH3:5])[CH3:2].Cl[CH2:22][C:23](=O)[CH3:24].[C:26]([O-])(O)=O.[Na+]>CCO.[Cl-].[Cl-].[Zn+2]>[CH2:4]([CH:3]([C:6]1[C:7]2[N:8]([CH:22]=[C:23]([CH3:24])[CH:26]=2)[N:9]=[C:10]([O:12][CH3:13])[CH:11]=1)[CH2:1][CH3:2])[CH3:5]

Komponenten

6

Edukt 3

HCID 6571ChloroacetoneHCID 516892Sodium BicarbonateHCID 68840437N-[4-(1-Ethyl-propyl)-6-methoxy-pyridazin-3-yl]-2,2-dimethyl-propionamide

Produkt 1

HCID 688419544-(1-Ethyl-propyl)-2-methoxy-6-methyl-pyrrolo[1,2-b]pyridazineAusbeute 11 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3007855ZincchlorideKatalysatorHCID 702EthanolLösungsmittel

Versuchsvorschrift

A solution of N-[4-(1-ethyl-propyl)-6-methoxy-pyridazin-3-yl]-2,2-dimethyl-propionamide (5.32 g, 19.08 mmol) in EtOH (250 mL) is treated with ZnCl2 (26.0 g, 190.8 mmol) and refluxed for 48 h. The reaction is cooled to rt and concentrated. The residue is taken up with EtOAc (250 mL), and H2O (100 mL). It is washed with H2O (2×100 mL); dried with Na2SO4; filtered and concentrated. The residue is then dissolved in EtOAc (80 mL), reacted with chloroacetone (1.6 mL, 20.03 mmol.) at reflux overnight. While it is hot, NaHCO3 (8.10 g) is added and the reaction is refluxed for 1 h. It is cooled to rt and filtered through silica gel washed with EtOAc and concentrated. Purification of the crude material by chromatography gives the title compound (0.48 g, 2.07 mmol, 11%). 1H NMR (CDCl3): δ. 0.84 (t, J=7.5 Hz, 6H), 1.69-1.869 (m, 4H), 2.45 (s, 3H), 3.19-3.30 (m, 1H), 3.94 (s, 3H), 6.39 (s, 1H), 7.49 (s, 1H). ES-MS (m/z): calcd for C14H20N2O (M+H)+: 233.3; found: 234.1.

Aufarbeitung

  1. temperaturerefluxed for 48 h
  2. concentrationconcentrated
  3. washIt is washed with H2O (2×100 mL)
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue is then dissolved in EtOAc (80 mL)
  8. temperatureat reflux overnight
  9. temperaturethe reaction is refluxed for 1 h
  10. temperatureIt is cooled to rt
  11. filtrationfiltered through silica gel
  12. washwashed with EtOAc
  13. concentrationconcentrated
  14. customPurification of the crude material by chromatography

Quellen und Nachweise

ORD-Eintrag
ord-bb5c024b94f041ca9f0a334f734cb00f
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07612067B2

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