Reaction #156391

Reaction equation

5,7-Difluoro-6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline

HCl

→

title compound

2-{4-[3-(5,7-Difluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-ethanol

Solvents

DCM

dioxane

Conditions

Workup

1. 1
   Otherthe solvent was removed
2. 2
   Washwashed with saturated NaHCO3 and brine
3. 3
   DryingThe organic layer was dried over Na2SO4
4. 4
   Otherthe solvent was removed
5. 5
   OtherThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
6. 6
   OtherThe solvent was removed
7. 7
   workup.ADDITIONthe residue was diluted in MeOH
8. 8
   Otherto remove the TFA salt
9. 9
   OtherThe filtrate was evaporated

Procedure

5,7-Difluoro-6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline (Stage 170.1, 82.2 mg, 0.168 mmol) was dissolved in DCM (2 mL) and a solution of 4 N HCl in dioxane (0.126 mL) was added. The RM was stirred at rt for 1 h and the solvent was removed. It was then taken up with EtOAc and washed with saturated NaHCO3 and brine. The organic layer was dried over Na2SO4 and the solvent was removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The solvent was removed and the residue was diluted in MeOH. The solution was passed through an SPE cartridge of HCO3− to remove the TFA salt. The filtrate was evaporated to give the free salt of the title compound (tR 0.8 min (conditions 2), MH+=407, 1H-NMR in DMSO-d6: 8.92 (dd, 1H); 8.51 (d, 1H); 8.38 (s, 1H); 8.06 (t, 2H); 7.72 (d, 1H); 7.59 (dd, 1H); 7.57 (s, 1H); 7.51 (d, 1H); 4.55 (s, 2H); 4.20 (t, 2H); 3.78-3.73 (m, 2H), 3.13 (s, 1H)).

Source