Reaktion #156350

Reaktionsgleichung

Iodine

H3PO2

(rac)-Imidazo[1,2-a]pyridin-6-yl-[6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-methanol

→

title compound

3-Imidazo[1,2-a]pyridin-6-ylmethyl-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

Lösungsmittel

water

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionextracted with EtOAc
2. 2
   SonstigeThe organic layer was separated
3. 3
   Waschenwashed with 10% Na2CO3-sol
4. 4
   Sonstigethen dried on Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated
7. 7
   Extraktionagain extracted with DCM containing little MeOH
8. 8
   SonstigeOrganic layers were evaporated
9. 9
   Extraktionboth crudes from the two extractions
10. 10
    Sonstigewere purified together by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=95:5->80:20)
11. 11
    workup.ADDITIONThe fractions containing the product
12. 12
    Sonstigewere evaporated
13. 13
    Filtrationpentane, filtered
14. 14
    Sonstigedried under high vacuum

Vorschrift

Iodine (50.8 mg, 0.2 mmol) and H3PO2 (0.11 mL of a 50% aqueous solution, 1.0 mmol) were added to a solution of (rac)-Imidazo[1,2-a]pyridin-6-yl-[6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-methanol (Example 9, 34.5 mg, 0.1 mmol) in acetic acid (0.5 mL). The RM was heated at 150° C. for 1 h. The RM was diluted with water and extracted with EtOAc. The organic layer was separated and washed with 10% Na2CO3-sol then dried on Na2SO4, filtered and concentrated. Combined aqueous layers were completely neutralized and again extracted with DCM containing little MeOH. Organic layers were evaporated and both crudes from the two extractions were purified together by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=95:5->80:20). The fractions containing the product were evaporated and the residue taken in EtOAc and pentane, filtered and dried under high vacuum to afford the title compound as beige crystals (tR 2.70 min (conditions 3), MH+=330.2, 1H-NMR in DMSO-d6: 8.58 (s, 1H); 8.44 (s, 1H); 8.12 (s, 1H); 8.08 (d, 1H); 7.90 (s, 1H); 7.62 (s, 1H); 7.54-7.44 (m, 3H); 7.22 (d, 1H); 4.31 (s, 2H); 3.90 (s, 3H)).

Quelle