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 300 ml round bottom lfask was charged with a magnetic stir bar, toluene (39 ml), 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine (1.1 g, 3.51 mmol), Pd2(dba)3 (0.321 g, 0.35 mmol), 2-(DIMETHYLAMINO)-2'-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (0.414 g, 1.05 mmol), SODIUM TERT-BUTOXIDE (1.011 g, 10.52 mmol), and (1-methylpiperidin-4-yl)methanamine (0.674 g, 5.26 mmol). The mixture was degassed with N2, the vessel fitted with a reflux condenser, and then placed in an oil bath heated to 110 °C for 16hrs. The mixture was cooled to r.t, filtered throught a bed of celite, washed with methanol, the filtrate was concentrated, the residue was pre-absorbed onto silca gel (~10g) and purified with ISCO (eluent methanol/DCM (1/3) to afford the title compound N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine (0.510 g, 35.9 %). (Note: the ligand I used was old) (note: tried direct displacement under microwave radiation at 180°C in 4MHCl or KOtBu in methoxyethanol; both condition didn't result in the desired product).

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