CN1CCC(CN)CC1.Cl.FC(F)(F)Oc1cccc(-c2cnc3ccc(Cl)nn23)c1>CC(C)(C)[O-].CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1.Cc1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd].[Pd]>CN1CCC(CNc2ccc3ncc(-c4cccc(OC(F)(F)F)c4)n3n2)CC1A 100 mL round bottom flask was charged with a magnetic stir bar, toluene (17.45 mL), 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine hydrochloride (550 mg, 1.57 mmol) (EN02141-06), Pd2dba3 (144 mg, 0.16 mmol), 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (185 mg, 0.47 mmol),sodium tert-butoxide (604 mg, 6.28 mmol), and (1-methylpiperidin-4-yl)methanamine (302 mg, 2.36 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 (~ 10 g) and purified on silica gel (80 g) using MeOH/DCM (1:3) as eluent to afford the title compound, .N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine (391 mg, 55.6 %) as an off white solid. 110 mg of this pure free base was dissolved in anhydrous MeOH and 32 uL of conc. H2SO4 were added. The mixture was stirred for 10 min. ar rt before being conc. in vacuo. The crude solids were triturated with diethyl ether and collected via vacuum filtration to afford the title compound as its bis(bisulfate).
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