反应详情

tert-butyl-4-(2-(3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenoxy)ethyl)piperazine-1-carboxylate (25 mg, 0.042 mmol) was dissolved in dichloromethane (5 mL) that had been saturated by bubbling HCl gas. The solution was stirred at room temperature for 2 h. The solvent was concentrated in vacuo. The residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 10% acetonitrile/90% water (0.1% TFA, v/v) initially, proceeding to 60% acetonitrile/40% water (0.1% TFA, v/v) in a linear fashion over 9 min) to give N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)-6-(3-(2-(piperazin-1-yl)ethoxy)phenyl)imidazo[1,2-b]pyridazin-8-amine hydrochloride (15 mg, 71%) as a yellow solid. 1H NMR (300 MHz, DMSO+D2O): δ 9.12 (s, 1H), 8.49 (s, 1H), 8.21 (s, 1H), 7.58-7.52 (m, 4 h), 7.27-7.26 (m, 1H), 6.66 (d, 1H, J=7.8 Hz), 6.19 (d, 1H, J=8.4 Hz), 4.51 (brs, 2H), 4.25 (brs, 1H), 3.69-3.37 (m, 12H), 2.08-1.99 (m, 3H), 1.72 (brs, 1H), 1.12 (d, 3H, J=6.3 Hz). LC/MS: 499 [M+H]+, tR=1.08 min. HPLC: 99.25% at 214 nm, 99.12% at 254 nm, tR=4.99 min.

1. customby bubbling HCl gas
2. concentrationThe solvent was concentrated in vacuo
3. customThe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
4. waitgradient conditions: 10% acetonitrile/90% water (0.1% TFA, v/v) initially, proceeding to 60% acetonitrile/40% water (0.1% TFA, v/v) in a linear fashion over 9 min