Cesium carbonate → 7-Fluoro-6-(6-{1-[1-(2,2,2-trifluoro-ethyl)-piperidin-4-yl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline

Participants

Reaction Conditions

Reaction Steps

A mixture of 7-fluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline (Example 180, 50 mg, 0.117 mmol), 2,2,2-trifluoroethyl methanesulfonate (55 μL, 0.468 mmol) and Cs2CO3 (76 mg, 0.234 mmol) in THF (1 mL) was stirred at 70° C. for 2 h. 2,2,2-trifluoroethyl methanesulfonate (69 μL, 0.585 mmol) was then added and the RM was stirred at reflux for 24 h. 2,2,2-trifluoroethyl methanesulfonate (69 μL, 0.585 mmol) was added again and the RM was stirred at reflux for 18 h more. The mixture was diluted with EtOAc and washed with NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with a 4 g RediSep® silica gel column, DCM/(DCM/MeOH 19:1)=100:0→0:100) to afford the title compound (tR 3.74 min (conditions 3), 1H-NMR in DMSO-d6: 8.85 (m, 1H); 8.54 (s, 1H); 8.34 (d, 1H); 8.07 (m, 3H); 7.77 (d, 1H); 7.61 (s, 1H); 7.54 (d, 1H); 7.47 (dd, 1H); 4.55 (s, 2H); 4.39 (m, 1H); 3.67 (m, 2H); 2.94 (m, 4H); 2.16 (m, 2H); 2.00 (m, 2H)).

Provenance & Evidence