Reaktion #156461

Reaktionsgleichung

NaOH

Iodide

(rac)-6-Chloro-3-[1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (rac)-1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethanol

H3PO2

→

title compound

(rac)-3-[1-(6-Fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

Lösungsmittel

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONintroduced in 4 microwave reactors
2. 2
   workup.ADDITIONwere then added into each reactor
3. 3
   Sonstigeirradiations 5 min
4. 4
   Sonstigeat 150° C
5. 5
   Extraktionextracted twice with EtOAc
6. 6
   Waschenwashed with brine
7. 7
   Trocknendried over Na2SO4
8. 8
   Sonstigethe solvent was removed
9. 9
   SonstigeThe residue was purified by flash chromatography (CombiFlash® Companion System®, with 120 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 30 min)
10. 10
    workup.ADDITIONThe collected fractions containing product
11. 11
    Sonstigewere evaporated
12. 12
    Sonstigethe residue was dried under vacuum

Vorschrift

(rac)-6-Chloro-3-[1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (rac)-1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethanol (Stage 278.2, 2 g, 5.78 mmol) was dissolved in acetic acid (80 mL) and introduced in 4 microwave reactors. Iodide (1.84 g×4, 29 mmol), followed by H3PO2 50% (2.36 mL×4, 87 mmol) were then added into each reactor. Then they were submitted to microwave irradiations 5 min at 150° C. After combination, it was basified by a 2.5 M NaOH solution and extracted twice with EtOAc. The organics were joined and washed with brine, dried over Na2SO4 and the solvent was removed. The residue was purified by flash chromatography (CombiFlash® Companion System®, with 120 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 30 min). The collected fractions containing product were evaporated and the residue was dried under vacuum to afford the title compound (tR 1.15 min (conditions 2), MH+=330).

Quelle