N-(4-Methoxybenzyl)pyridin-2-amine → 6-chloro-N-(3-fluoropyridin-4-yl)-8-((4-methoxybenzyl)(pyridin-2-yl)amino)imidazo[1,2-b]pyridazine-3-carboxamide

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To a suspension containing a mixture of 6,8-dichloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide and 8-bromo-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide 5A (1.2 g, 3.68 mmol) was added N-(4-methoxybenzyl)pyridin-2-amine (1.183 g, 5.52 mmol) in THF (36.8 mL) at 0° C. This mixture was charged with a 1M solution of potassium tert-butoxide (7.36 mL, 7.36 mmol), slowly via syringe. The dark suspension was stirred for 20 min at room temperature. Volatiles were removed in vacuo and the resulting residue was triturated with MeOH and cooled to 0° C. Filtration, with cold MeOH washes afforded a tan solid which was dissolved in THF and azeotroped with PhMe to remove residual MeOH, then dried in vacuo overnight, which afforded 6-chloro-N-(3-fluoropyridin-4-yl)-8-((4-methoxybenzyl)(pyridin-2-yl)amino)imidazo[1,2-b]pyridazine-3-carboxamide (1.31 g, 68.5% yield) as a tan solid. LC/MS, m/z 504.0 (M+1). HPLC Rt=4.265 min. YMC S5 ODS-A column (4.6×50 mm) 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.2% H3PO4). Solvent A: (10% MeOH, 90% H2O, 0.2% H3PO4). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% 1 min, flow rate 4 mL/min. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.02 (1H, d, J=2.27 Hz), 8.62 (1H, d, J=2.27 Hz), 8.35-8.48 (4H, m), 8.23 (1H, s), 7.67-7.83 (1H, m), 7.32 (2H, dd, J=8.56, 2.27 Hz), 7.24 (1H, dd, J=7.05, 5.29 Hz), 7.00 (1H, s), 6.79-6.89 (2H, m), 5.60 (2H, s), 3.62-3.72 (3H, s).

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