Reaction #156465

Reaction equation

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

HCl

→

title compound

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

Solvents

DCM

dioxane

Conditions

Workup

1. 1
   OtherThe solvent was totally evaporated
2. 2
   Washwashed with saturated NaHCO3 and brine
3. 3
   DryingThe organic layer was dried over Na2SO4 and solvent
4. 4
   Otherevaporated under vacuo
5. 5
   OtherThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
6. 6
   OtherThe acetonitrile was removed
7. 7
   ExtractionIt was extracted 3 times with EtOAc
8. 8
   Washwashed with brine
9. 9
   DryingIt was dried over Na2SO4
10. 10
    Otherthe solvent was removed
11. 11
    OtherThe residue was triturated with pentane
12. 12
    Filtrationthe precipitate was filtered off

Procedure

3-(6-Fluoro-1-methyl-1H-indazol-5-yl methyl)-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine (Stage 281.1, 269 mg, 566 μmol) was dissolved in DCM (5 mL). HCl in dioxane (4 N, 283 μl) was added and the RM was stirred 1 h at rt. The solvent was totally evaporated and the residue was taken up with EtOAc and washed with saturated NaHCO3 and brine. The organic layer was dried over Na2SO4 and solvent evaporated under vacuo. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The acetonitrile was removed and the aqueous solution was basified with 5% NaHCO3. It was extracted 3 times with EtOAc and then the organics were joined and washed with brine. It was dried over Na2SO4 and the solvent was removed. The residue was triturated with pentane and the precipitate was filtered off to give the title compound a white solid (tR 0.93 min (conditions 2), MH+=392, 1H-NMR in DMSO-d6: 8.42 (s, 1H); 8.1 (s, 1H); 8.02 (d, 1H); 7.97 (s, 1H); 7.75 (d, 1H); 7.52 (t, 3H); 4.95 (m, 1H); 4.40 (s, 2H); 4.21 (t, 2H); 3.96 (s, 3H); 3.77 (m, 2H)).

Source