Reaction #156476

Reaction equation

DMF

POCl3

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

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

→

6-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-imidazo[1,2-a]pyridine-3-carbaldehyde

Solvents

water

Conditions

Workup

1. 1
   TemperatureThe RM was warmed up to 120° C.
2. 2
   workup.STIRRINGstirred for 2 h
3. 3
   TemperatureIt was cooled down to rt
4. 4
   ExtractionIt was extracted twice with EtOAc
5. 5
   WashCombined organic layers was washed with brine
6. 6
   Dryingdried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated
9. 9
   OtherThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM)
10. 10
    Otherto afford
11. 11
    Otherafter evaporation of the solvent the title compound as a yellow solid (tR 0.7 min (conditions 2), MH+=358)

Procedure

DMF (2 mL) was cooled down to 0° C. and then POCl3 (0.130 mL, 1.397 mmol) was added slowly. The solution was stirred for 10 min then it was warmed up to rt and the 3-(imidazo[1,2-a]pyridin-6-ylmethyl)-6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazine (Example 10, 200 mg, 0.607 mmol) was introduced. The RM was warmed up to 120° C. and stirred for 2 h. It was cooled down to rt and water was added. It was extracted twice with EtOAc. Combined organic layers was washed with brine and dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM) to afford after evaporation of the solvent the title compound as a yellow solid (tR 0.7 min (conditions 2), MH+=358).

Source