反应详情

温度

100 °C

A mixture of 8-bromo-6-phenylimidazo[1,2-b]pyridazine (0.15 g, 0.55 mmol), (S)-6-(2-methylpyrrolidin-1-yl)pyridin-2-amine (0.107 g, 0.61 mmol), Pd2(dba)3 (32 mg, 0.055 mmol), BINAP (68 mg, 0.11 mmol) and Cs2CO3 (0.54 g, 1.65 mmol) in dioxane (20 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated and the residue purified by chromatography (silica gel, 20 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15) to afford (S)—N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine (51 mg, 25%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.83 (s, 1H), 7.99 (s, 1H), 7.95-7.91 (m, 2H), 7.59 (s, 1H), 7.51-7.40 (m, 4 h), 6.29 (d, 1H, J=7.5 Hz), 6.08 (d, 1H, J=8.1 Hz), 4.28-4.24 (m, 1H), 3.64-3.60 (m, 1H), 3.48-3.40 (m, 1H), 2.18-2.10 (m, 3H), 1.78-1.75 (m, 1H), 1.19 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 371, tR=2.015 min, HPLC: 99.09% at 214 nm, 99.69% at 254 nm, tR=4.691 min.

1. concentrationthen concentrated
2. customthe residue purified by chromatography (silica gel, 20 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15)