Reaction Steps
A mixture of 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (300 mg, 0.91 mmol), 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinoline (354 mg, 1.37 mmol), Pd2(dba)3 (105 mg, 0.18 mmol), X-phos (172 mg, 0.36 mmol) and Na2CO3 (290 mg, 2.73 mmol) in dioxane (5 mL) and water (5 mL) was heated to 100° C. for 15 h then concentrated in vacuo and purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=1:1) to afford the desired product as its free base. 1 mL HCl was added to the residue and the mixture stirred for 5 min. The mixture was then concentrated to give N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)-6-(1,2,3,4-tetrahydroquinolin-7-yl)imidazo[1,2-b]pyridazin-8-amine hydrochloride (25 mg, 6%). 1H NMR (300 MHz, DMSO): δ 10.74 (s, 1H), 9.14 (s, 1H), 8.55 (s, 1H), 8.30 (s, 1H), 7.51 (t, 1H, J=7.8 Hz), 7.35-7.19 (m, 3H), 6.67 (d, 1H, J=7.8 Hz), 6.16 (d, 1H, J=8.1 Hz), 4.23-4.20 (m, 2H), 3.65-3.58 (m, 1H), 3.42-3.38 (m, 3H), 2.83-2.79 (m, 2H), 2.10-1.91 (m, 5H), 1.72-1.70 (m, 1H), 1.13 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 426, tR=1.923 min, HPLC: 99.64% at 214 nm, 99.62% at 254 nm, tR=6.052 min.
