Cesium carbonate → Methyl 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate

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Reaction Conditions

Reaction Steps

A mixture of methyl 4-(8-bromoimidazo[1,2-b]pyridazin-6-yl)benzoate (208 mg, 0.63 mmol), 6-(2-methylpyrrolidin-1-yl)pyridin-2-amine (168 mg, 0.95 mmol), Pd2(dba)3 (37 mg, 0.063 mmol), BINAP (157 mg, 0.252 mmol), Cs2CO3 (616 mg, 1.89 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, CH2Cl2:MeOH=30:1) to give methyl 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo [1,2-b]pyridazin-6-yl)benzoate (120 mg, 45%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.81 (s, 1H), 8.09-7.98 (m, 5H), 7.59 (d, 1H, J=1.5 Hz), 7.42 (t, 1H, J=8.4 Hz), 6.27 (d, 1H, J=7.5 Hz), 6.08 (d, 1H, J=8.1 Hz), 4.29-4.21 (m, 1H), 3.96 (s, 3H), 3.62-3.58 (m, 1H), 3.43-3.40 (m, 1H), 2.16-2.12 (m, 3H), 1.78-75 (m, 1H), 1.19 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 429, tR=1.989 min, HPLC: 94.6% at 214 nm, 96.8% at 254 nm, tR=5.255 min.

Provenance & Evidence