Ammonia → (S)-3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide

Participants

Reaction Steps

To a stirred solution of (S)-3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (76 mg, 0.195 mmol), HOBT (39 mg, 0.289 mmol), Et3N (39 mg, 0.786 mmol) and EDCI (55 mg, 0.289 mmol) in dichloromethane (20 mL) and dioxane (10 mL) was bubbled NH3 gas until saturation and the mixture stirred for 16 h at room temperature. The reaction mixture was filtered then 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)-3-(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 8.93 (s, 1H), 8.47 (s, 1H), 8.14 (d, 1H, J=8.1 Hz), 8.03-7.97 (m, 2H), 7.63-7.58 (m, 2H), 7.44 (t, 1H, J=8.1 Hz), 6.30 (d, 1H, J=7.8 Hz), 6.09 (d, 1H, J=8.1 Hz), 4.32-4.22 (m, 1H), 3.69-3.61 (m, 1H), 3.48-3.42 (m, 1H), 2.17-2.01 (m, 3H), 1.68 (s, 1H), 1.17 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 414, tR=1.594 min, HPLC: 100% at 214 nm, 100% at 254 nm, tR=4.417 min.

Provenance & Evidence