反应详情

A mixture of 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (83 mg, 0.2 mmol), N1,N1-dimethylethane-1,2-diamine (19 mg, 0.22 mmol), 1-methyl-1H-imidazole (66 mg, 0.8 mmol) and EDCI (153 mg, 0.8 mmol) in dichloromethane (10 mL) was stirred at room temperature for 16 h then concentrated. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, methanol:dichloromethane=1:20) and further purified by Prep-TLC (silica gel, methanol:dichloromethane=1:10) to afford N-(2-(dimethylamino)ethyl)-3-(8-(6-(2-methylpyrrolidin-1-yl)pyridine-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide (41 mg, 42%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.89 (s, 1H), 8.48 (s, 1H), 8.13 (dd, 1H, J1=6.9 Hz, J2=1.8 Hz), 8.02-7.97 (m, 2H), 7.65-7.60 (m, 2H), 7.45 (t, 1H, J=8.1 Hz), 6.31 (d, 1H, J=7.5 Hz), 6.10 (d, 1H, J=8.1 Hz), 4.29-4.25 (m, 1H), 3.76-3.72 (m, 2H), 3.66-3.60 (m, 1H), 3.54-3.40 (m, 1H), 3.19-3.15 (m, 2H), 2.81 (s, 6H), 2.25-2.00 (m, 3H), 1.75-1.73 (m, 1H), 1.17 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 485, tR=1.062 min, HPLC: 99.08% at 214 nm, 99.16% at 254 nm, tR=4.868 min.

1. concentrationthen concentrated
2. customThe residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, methanol:dichloromethane=1:20)
3. customfurther purified by Prep-TLC (silica gel, methanol:dichloromethane=1:10)