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 (120 mg, 0.365 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (134 mg, 0.547 mmol), Pd2(dba)3 (21 mg, 0.037 mmol), X-phos (70 mg, 0.146 mmol) and Na2CO3 (117 mg, 1.1 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 first purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1), and then again (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1) to give 6-(1H-indazol-6-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (37 mg, 25%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 13.31 (s, 1H), 9.69 (s, 1H), 8.87 (s, 1H), 8.23 (s, 1H), 8.17 (s, 1H), 8.03 (s, 1H), 7.91 (d, 1H, J=8.4 Hz), 7.69-7.67 (m, 2H), 7.45 (t, 1H, J=7.8 Hz), 6.75 (d, 1H, J=7.8 Hz), 6.08 (d, 1H, J=8.1 Hz), 4.21 (brs, 1H), 3.58 (brs, 1H), 3.45-3.38 (m, 1H), 2.06-1.97 (m, 3H), 1.69 (brs, 1H), 1.11 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 411, tR=1.672 min, HPLC: 95.88% at 214 nm, 98.36% at 254 nm, tR=5.913 min.

1. customThe solvent was removed in vacuo
2. customthe resulting mixture was first purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1)