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

HRID 1432712ノート

反応式

HRID 1432712 の反応式
[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]

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 3007855Zincchloride触媒HCID 702Ethanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-bb5c024b94f041ca9f0a334f734cb00f
出典データセット
uspto-grants-2009_11
特許番号
US07612067B2

反応ノート

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