1-Methylimidazole → 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(1-methyl-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 (50 mg, 0.265 mmol), 4-(2-aminoethyl)-1-methylpyridin-2(1H)-one hydrochloride (16 mg, 0.132 mmol), 1-methyl-1H-imidazole (118 mg, 1.45 mmol) and EDCI (276 mg, 1.45 mmol) in dichloromethane (10 mL) and DMF (3 mL) was stirred at room temperature for 16 h then extracted with ethyl acetate (50 mL). The combined extracts were washed with water (5 mL×2), then brine (5 mL×2). After drying and concentration, the residue was purified by chromatography (silica gel, 5 g, 200˜300 mesh, methanol:dichloromethane=1:30) to afford 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)ethyl)benzamide (27 mg, 21%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.94 (s, 1H), 8.67 (s, 1H), 8.53 (s, 1H), 8.20 (s, 1H), 8.03-7.94 (m, 4 h), 7.66 (s, 1H), 7.58 (d, 1H, J=6.6 Hz), 7.41 (d, 1H, J=8.4 Hz), 7.11 (d, 1H, J=8.4 Hz), 6.23 (s, 1H), 6.13 (d, 1H, J=7.2 Hz), 4.01 (s, 3H), 3.77 (s, 3H), 3.53-3.47 (m, 2H), 3.36 (s, 3H), 2.69 (t, 2H, J=6.6 Hz). LC-MS: [M+H]+, 526, tR=1.367 min, HPLC: 98.9% at 214 nm, 99.36% at 254 nm, tR=4.615 min.

Provenance & Evidence