1-Methylimidazole → 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(2-oxo-1,2-dihydropyridin-4-yl)ethyl)benzamide

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Reaction Steps

A mixture of 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (76 mg, 0.195 mmol), 4-(2-aminoethyl)pyridin-2(1H)-one (64 mg, 0.215 mmol), 1-methyl-1H-imidazole (96 mg, 1.17 mmol) and EDCI (223 mg, 1.17 mmol) in dichloromethane (10 mL) and DMF (0.5 mL) was stirred at room temperature for 16 h then dichloromethane (20 mL) was added. The mixture was washed with water (2×2 mL) and brine (2×2 mL) then dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, MeOH:dichloromethane=1:10) to afford 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(2-oxo-1,2-dihydropyridin-4-yl)ethyl)benzamide (44 mg, 44%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 11.35 (s, 1H), 9.94 (s, 1H), 8.67 (s, 1H), 8.52 (s, 1H), 8.19 (s, 1H), 8.02-7.93 (m, 4 h), 7.66 (s, 1H), 7.40 (d, 1H, J=8.4 Hz), 7.26 (d, 1H, J=6.6 Hz), 7.10 (d, 1H, J=8.1 Hz), 6.16 (s, 1H), 6.08 (d, 1H, J=6.3 Hz), 4.00 (s, 3H), 3.76 (s, 3H), 3.50-3.40 (m, 2H), 2.69-2.67 (m, 2H). LC-MS: [M+H]+, 512, tR=1.412 min, HPLC: 98.19% at 214 nm, 97.49% at 254 nm, tR=7.244 min.

Provenance & Evidence