1-Methylpiperidine-4-methylamine → N-[(1-methylpiperidin-4-yl)methyl]-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazin-6-amine

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A 50 mL round bottom flask was charged with a magnetic stir bar, toluene (6.376 mL), 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine hydrochloride (200 mg, 0.57 mmol), (1-methylpiperidin-4-yl)methanamine (110 mg, 0.86 mmol), 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (67.4 mg, 0.17 mmol), Pd2dba3 (52.3 mg, 0.06 mmol), and sodium tert-butoxide (220 mg, 2.28 mmol). The mixture was degassed with argon, the vessel fitted with a reflux condenser, and then placed in an oil bath heated to 110 °C with stirring for 16 h. The mixture was cooled to rt, pre-absorbed onto silca gel (~ 20 g) and purified on silica gel (80 g) using MeOH/DCM (1:3) as eluent to afford the title compound ~ 90 % pure. This material was then dissolved in DMSO and purified via reverse phase HPLC water/MECN (5->55%, 12 min) as eluent. The pure fractions were collected and converted to the corresponding HCl salt to afford N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine (125 mg, 49.5 %) hydrochloride as a white solid.

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