Cesium carbonate → (R)-N-(6-(2-methylpyrrolidin-1-yl)pyridine-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine

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Reaction Conditions

Reaction Steps

A mixture of 8-bromo-6-phenylimidazo[1,2-b]pyridazine (166 mg, 0.6 mmol), (R)-6-(2-methylpyrrolidin-1-yl)pyridin-2-amine (160 mg, 0.9 mmol), Pd2(dba)3 (36 mg, 0.06 mmol), BINAP (152 mg, 0.24 mmol), Cs2CO3 (593 mg, 1.8 mmol) and dioxane (10 mL) was heated to 100° C. with stirring for 16 h under N2. The solvent was removed in vacuo and the resulting mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1) to give (R)—N-(6-(2-methylpyrrolidin-1-yl)pyridine-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine (78 mg, 35%) as a white solid. 1H NMR (300 MHz, DMSO): δ 8.76 (s, 1H), 7.95-7.87 (m, 3H), 7.55-7.35 (m, 5H), 6.23 (d, 1H, J=7.5 Hz), 6.02 (d, 1H, J=8.1 Hz), 4.22-4.18 (m, 1H), 3.57-3.53 (m, 1H), 3.41-3.36 (m, 1H), 2.09-1.98 (m, 3H), 1.72 (brs, 1H), 1.16 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 371, tR=1.994 min, HPLC: 99.27% at 214 nm, 99.26% at 254 nm, tR=4.72 min.

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