Ammonia → (S)-4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide

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Reaction Steps

To a stirred solution of (S)-4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (90 mg), HOBT (49 mg, 0.365 mmol), Et3N (49 mg, 0.486 mmol) and EDCI (70 mg, 0.365 mmol) in dichloromethane (20 mL) and dioxane (100 mL) was bubbled NH3 gas until saturation and the mixture stirred for 16 h at room temperature. The mixture was filtered and the filtrate concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200-300 mesh, MeOH:dichloromethane=1:50) to afford (S)-4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide (38 mg, 47%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.74 (s, 1H), 7.94-7.86 (m, 5H), 7.49 (s, 1H), 7.32 (t, 1H, J=8.1 Hz), 6.18 (d, 1H, J=6.0 Hz), 5.98 (d, 1H, J=8.4 Hz), 4.17-4.14 (m, 1H), 3.55-3.49 (m, 1H), 3.38-3.32 (m, 1H), 2.07-1.93 (m, 3H), 1.68 (s, 1H), 1.10 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 414, tR=1.505 min, HPLC: 97.48% at 214 nm, 97.67% at 254 nm, tR=6.027 min.

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