反应详情

To a solution of (rac)-7-fluoro-6-[1-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-quinoline (Stage 255.1, 49 mg, 0.101 mmol) in DCM (3 mL) stirred at rt was added a solution of HCl in dioxane (4 M, 0.252 mL). The RM was stirred 1 h at rt, during this time the product precipitated as an oil. The residue was taken in DCM and water, then neutralized with a solution of 10% NaHCO3 and extracted with DCM. The combined organic phase was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, EtOAc/MeOH (1% NH3)=100:0->80:20) to afford the title compound as a white crystalline powder (tR 3.40 min (conditions 3), MH+=403.3, 1H-NMR in DMSO-d6: 8.81 (d, 1H), 8.35-8.28 (m, 2H); 8.05 (d, 1H); 7.95-7.88 (m, 2H), 7.76 (d, 1H); 7.72 (s, 1H); 7.49 (d, 1H); 7.46-7.40 (m, 1H); 5.03 (q, 1H); 4.92 (t, 1H); 4.15 (t, 2H); 3.72 (q, 2H); 2.83 (d, 3H)).

1. customprecipitated as an oil
2. extractionextracted with DCM
3. dry with materialThe combined organic phase was dried over MgSO4
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, EtOAc/MeOH (1% NH3)=100:0->80:20)