A solution of 1-BOC-3-methyl-5-bromo-indazole (0.24 g, 0.76 mmol), in DMF (10 mL) at room temperature, under nitrogen and treated with potassium acetate (0.40 g, 4 mmol), bis(pinacolato)diboron (0.38 g, 1.5 mmol) and Pd(dppf)Cl2.CH2Cl2 (80 mg, 0.1 mmol). This suspension was degassed with four cycles of vacuum and nitrogen. The suspension was heated at 80° C. for two hours and then cooled to room temperature. The suspension was treated with 3-(3-bromo-imidazo[1,2-b]pyridazine-6-yl-amino)-piperidine-1-carboxylic acid tert-butyl ester (0.31 g, 0.76 mmol) and potassium carbonate (0.40 g) and water (2 mL), degassed (vacuum and then nitrogen×4) and heated at 100° C. for 2 hours. The reaction mixture was cooled to room temperature, quenched with saturated aqueous sodium bicarbonate (100 mL) and extracted with ethyl acetate (3×50 mL). The organic layers were combined, dried with anhydrous magnesium sulfate, filtered and evaporated. After chromatography with silica gel and a gradient of hexane/ethyl acetate a mixture of mono and di-BOC protected material was obtained as shown by MS m/z 448 and 548. This mixture was treated with aqueous HCl (20%, double distilled, 5 mL) at room temperature overnight. Then the reaction mixture was evaporated to give [3-(3-methyl-1H-indazol-5-yl)-imidazo[1,2-b]pyridazine-6-yl]-piperidin-3-yl-amine trihydrochloride as an yellow solid (0.12 g, 34%); this material was purified by reversed phase chromatography (20.9 mg): mp decomposed above 250° C.; MS [M+H]+ m/z 348. Anal. (C19H21N7.3HCl.1.08H2O), C, H, N.
