Reaction #156464

Reaction equation

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

HCl

→

title compound

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

Solvents

DCM

dioxane

EtOAc

Conditions

Workup

1. 1
   Washwashed with a saturated NaHCO3 sol. The aqueous phase
2. 2
   Extractionwas extracted twice with EtOAc
3. 3
   WashThe combined organics were washed with brine
4. 4
   Dryingdried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Otherevaporated
7. 7
   OtherThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)

Procedure

(rac)-3-[1-(6-Fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine (Stage 279.1, 250 mg, 0.511 mmol) was dissolved in DCM (5 mL). HCl in dioxane (4 N, 0.5 mL) was added and the RM was stirred 1 h at rt. It was then diluted with EtOAc and washed with a saturated NaHCO3 sol. The aqueous phase was extracted twice with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA) to afford the title compound as a white solid (tR 0.98 min (conditions 2), MH+=406, 1H-NMR in DMSO-d6: 8.39 (s, 1H); 8.07 (d, 2H); 8.01 (d, 1H); 7.69 (s, 1H); 7.61 (s, 1H); 7.51 (d, 1H); 7.47 (d, 1H); 7.23 (d, 1H); 4.95 (t, 1H); 4.76 (q, 1H); 4.18 (t, 2H); 3.78 (s, 3H); 3.75 (q, 2H); 1.79 (d, 3H)).

Source