反应详情

A mixture of 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (45 mg, 0.11 mmol), 0.5 M ammonia in dioxane solution (23 mg, 1.3 mmol), EDCI (32 mg, 0.163 mmol) and HOBt (22 mg, 0.163 mmol) in dichloromethane (3 mL), DMF (0.5 mL) and Et3N (22 mg, 0.22 mmol) was stirred at room temperature for 16 h. The solution was concentrated in vacuo, washed with water (10 mL×3), and purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=30:1) to give 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide (13 mg, 29%) as a yellow oil. 1H NMR (300 MHz, DMSO): δ 9.68 (s, 1H), 8.82 (s, 1H), 8.44 (s, 1H), 8.23 (s, 1H), 8.12-7.99 (m, 5H), 7.68 (s, 1H), 7.48-7.43 (m, 2H), 6.74 (d, 1H, J=7.8 Hz), 6.09 (d, 1H, J=8.1 Hz), 4.26-4.21 (m, 1H), 3.58-3.40 (m, 2H), 2.09-2.00 (m, 3H), 1.74-1.70 (m, 1H), 1.15 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 414, tR=1.547 min, HPLC: 99.34% at 214 nm, 99.33% at 254 nm, tR=5.357 min.

1. concentrationThe solution was concentrated in vacuo
2. washwashed with water (10 mL×3)
3. custompurified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=30:1)