Reaktion #68508

Reaktionsgleichung

trimethylphosphine

THF

(6-(3,4,5-trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanol

(6-(3,4,5-Trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanamine

azidosodium

azidosodium

triethylamine

→

title compound

7-Methoxy-N-((6-(3,4,5-trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4-amine

Lösungsmittel

EtOAc

CH2Cl2

EtOAc

water

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe mixture was concentrated in vacuo (
2. 2
   Temperaturwithout 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
   Waschenwashed with water, brine
7. 7
   Filtration(back extract aq layer) and dry organic layer over Na2SO4, filter
8. 8
   Sonstigeevaporate
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
    Waschenwashed with NaHCO3 solution, sat. NaHCO3
12. 12
    Filtration(back extract aq layer), then dry organic layer over Na2SO4, filter
13. 13
    Sonstigeevaporate
14. 14
    SonstigeThe residue was purified via flash chromatography

Vorschrift

(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.

Quelle