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 (66 mg, 0.2 mmol), benzo[d][1,3]dioxol-5-ylboronic acid (60 mg, 0.24 mmol), Pd2(dba)3 (12 mg, 0.02 mmol), X-phos (39 mg, 0.08 mmol) and Na2CO3 (64 mg, 0.6 mmol) in dioxane (5 mL) and water (0.5 mL) was heated to 100° C. with stirring for 16 h under N2. The solvent was removed in vacuo and the resulting mixture was purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1) to give crude product as a yellow oil, which was then purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1) to give 6-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (62 mg, 75%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.58 (s, 1H), 8.69 (s, 1H), 8.14 (s, 1H), 7.61 (s, 1H), 7.44-7.39 (m, 3H), 7.06-7.04 (m, 1H), 6.70 (d, 1H, J=7.5 Hz), 6.11 (s, 2H), 6.05 (d, 1H, J=8.1 Hz), 4.27-4.20 (m, 1H), 3.58-3.53 (m, 1H), 3.41-3.36 (m, 1H), 2.07-1.99 (m, 3H), 1.71-1.68 (m, 2H), 1.14 (d, 1H, J=6.0 Hz). LC-MS: [M+H]+, 415, tR=1.965 min, HPLC: 99.31% at 214 nm, 99.64% at 254 nm, tR=6.821 min.

1. customThe solvent was removed in vacuo
2. customthe resulting mixture was purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1)
3. customto give crude product as a yellow oil, which
4. customwas then purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1)