반응 #68508

ord-c96f8d0c091e4e40bc3ad87e525d0f84

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    농축The mixture was concentrated in vacuo (
  2. 2
    온도without heating the flask) and the residue
  3. 3
    workup.DISSOLUTIONdissolved in DMF (2 mL)
  4. 4
    workup.WAITAfter 45 minutes
  5. 5
    workup.STIRRINGthe mixture stirred 1 h longer
  6. 6
    세척washed with water, brine
  7. 7
    여과(back extract aq layer) and dry organic layer over Na2SO4, filter
  8. 8
    기타evaporate
  9. 9
    workup.DISSOLUTIONThe azide intermediate was dissolved in THF (4 mL)
  10. 10
    workup.STIRRINGThe reaction mixture was stir at rt until the bubbling
  11. 11
    세척washed with NaHCO3 solution, sat. NaHCO3
  12. 12
    여과(back extract aq layer), then dry organic layer over Na2SO4, filter
  13. 13
    기타evaporate
  14. 14
    기타The residue was purified via flash chromatography

실험 절차

(6-(3,4,5-Trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanamine. To a suspension of (6-(3,4,5-trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanol (0.442 g, 1.6 mmol) in CH2Cl2 (5 mL) was added Mesyl-Cl (0.37 ml, 4.7 mmol) and triethylamine (0.66 ml, 4.7 mmol)-slight exotherm, place flask in water bath- and the mixture stirred at rt 1 h. The mixture was concentrated in vacuo (without heating the flask) and the residue dissolved in DMF (2 mL) and azidosodium (0.23 g, 3.5 mmol) was added in one portion. After 45 minutes, additional azidosodium (0.40 g, 6.0 mmol) was added and the mixture stirred 1 h longer. The mixture was diluted with EtOAc, washed with water, brine, (back extract aq layer) and dry organic layer over Na2SO4, filter and evaporate. The azide intermediate was dissolved in THF (4 mL) and trimethylphosphine 1M in THF (2.4 ml, 2.4 mmol) was added. The reaction mixture was stir at rt until the bubbling stops, plus an additional 2 minutes, then water (1 mL) was added. The mixture was diluted with EtOAc, washed with NaHCO3 solution, sat. NaHCO3, (back extract aq layer), then dry organic layer over Na2SO4, filter and evaporate. The residue was purified via flash chromatography using al % NH4OH in MeOH in CH2Cl2 gradient to afford the title compound as a tan solid.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08524900B2uspto-grants-2013_09