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 500 ml round bottom lfask was charged with a magnetic stir bar, toluene (200 ml), 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine (6.55 g, 20.88 mmol), Pd2dba3 (1.912 g, 2.09 mmol), fresh bottle of 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (2.465 g, 6.26 mmol), SODIUM TERT-BUTOXIDE (8.03 g, 83.53 mmol) and (1-methylpiperidin-4-yl)methanamine (4.55 g, 35.50 mmol). The mixture was degassed with N2, the vessel fitted with a reflux condenser, and then placed in an oil bath heated to 120 °C for 16hrs. The mixture was filtered throught a bed of celite, washed with methanol/DCM (3/1), the filtrate was concentrated, the residue was taken into a mixture of water and DCM/Isopropanol (5/1), separated, the water layer was extrated twice with DCM/isopropanol (5/1), the combined organics were dried (MgSO4), concentrated, the residue was pre- absorbed onto silca gel (~80g) and purified with ISCO (eluent methanol/DCM (1/3) to afford the title compound as which was taken into hexane, the solid was collected by filtration, washed with hexane, dried in vacum at 60°C to yield a light yellow solid as N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine (5.51 g, 62.9 %). 405mgs of the free base product was dissolved into 2ml of methanol, treated with 1M H2SO4 in methanol (1ml conc. H2SO4 + 17ml of methanol). The solution was stirred for 2min, solid crushed out, the suspension was continually stirred at r.t for overnight before being diluted with ethyl ether, the solid was collected by filtration, dried to yield a white solid as desired product- bi-sulfuric acid.

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