Reaction #156470

Reaction equation

3-(4,6-difluoro-1-methyl-1H-indazol-5-ylmethyl)-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine

HCl

NaHCO3

→

title compound

2-{4-[3-(4,6-Difluoro-1-methyl-1H-indazol-5-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-ethanol

Solvents

dioxane

dioxane

Conditions

Workup

1. 1
   Extractionthe aqueous phase was extracted with DCM
2. 2
   DryingThe combined organic phases were dried over MgSO4
3. 3
   Concentrationconcentrated under reduced pressure
4. 4
   OtherThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, hexane/EtOAc=100:0->80:20)

Procedure

To a solution of 3-(4,6-difluoro-1-methyl-1H-indazol-5-ylmethyl)-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine (Stage 285.1, 30 mg, 0.061 mmol) in dioxane (2 mL) stirred at 0° C. was added a solution of HCl in dioxane (4 M, 0.152 mL). The RM was stirred 1 h at rt, poured in a solution 10% NaHCO3, and the aqueous phase was extracted with DCM. The combined organic phases were dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, hexane/EtOAc=100:0->80:20) to afford the title compound as a white powder (tR 3.68 min (conditions 3), MH+=410.2, 1H-NMR in DMSO-d6: 8.38 (s, 1H); 8.19 (s, 1H); 8.06 (s, 1H); 8.04 (d, 1H); 7.53-7.46 (m, 3H); 4.97 (t, 1H); 4.40 (s, 2H); 4.18 (t, 2H); 3.97 (s, 3H); 3.76 (q, 2H)).

Source