反应详情

温度

100 °C

A mixture of 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (0.05 g, 0.152 mmol), 3-methoxyphenylboronic acid (0.025 g, 0.167 mmol), Pd2(dba)3 (0.017 g, 0.03 mmol), X-phos (0.029 g, 0.06 mmol) and Na2CO3 (0.048 g, 0.456 mmol) in dioxane (20 mL) and water (5 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:10) to afford 6-(3-methoxyphenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (25 mg, 41%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.76 (s, 1H), 7.95 (s, 1H), 7.56 (s, 1H), 7.47-7.32 (m, 4 h), 7.03-6.99 (m, 1H), 6.23 (d, 1H, J=7.5 Hz), 6.03 (d, 1H, J=8.4 Hz), 4.25-4.21 (m, 1H), 3.86 (s, 3H), 3.62-3.56 (m, 1H), 3.44-3.35 (m, 1H), 2.17-1.99 (m, 3H), 1.74-1.71 (m, 1H), 1.17 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 401, tR=1.961 min, HPLC: 95.06% at 214 nm, 98.71% at 254 nm, tR=7.643 min.

1. concentrationthen concentrated in vacuo
2. customThe residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:10)