反应详情

温度

40 °C

TFA (1 mL) was added to a 2 dram vial containing 6-((trans)-4-aminocyclohexylamino)-8-(4-methoxybenzylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide 39A and the mixture was heated at 40° C. After 40 min, the mixture was concentrated to dryness under a stream of nitrogen. The residue was dissolved in 3 mL of methanol and 3 mL of Solvent B (90% MeOH, 10% water, 0.1% TFA). One drop of TFA was added to the solution, the sample was split into 3 equal volumes and purified by reverse phase preparative HPLC on a Phenx Luna Axia Column 5u (21.2×100 mm) Solvent A (10% MeOH, 90% water, 0.1% TFA), Solvent B (90% MeOH, 10% water, 0.1% TFA) 10-80% solvent B gradient, 20 mL/min, 220 nM UV detection to provide 8-amino-6-(4-aminocyclohexylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (0.0419 g, 0.059 mmol, 15.44% yield). 1H NMR (500 MHz, CD3OD) δ ppm 8.65 (3H, d, J=7.15 Hz), 8.26 (3H, d, J=7.15 Hz), 8.08 (1H, s), 5.87 (1H, s), 3.66 (1H, m), 3.10 (1H, m), 2.22-2.27 (2H, m), 2.08 (2H, m), 1.53 (2H, m), 1.36-1.44 (2H, m). LC/MS: HPLC Retention time: 1.38 min, MS: 367 (M+1) (Shimidazu LC, Waters Sunfire C-18 column (4.65×50 mm, 5 um, 0-100% Solvent B, 4 min gradient, 4 mL/min, 220 UV detection. Solvent A: 10% MeOH/90% Water/0.1% TFA, Solvent B 90% MeOH/10% Water/0.1% TFA.)

1. concentrationthe mixture was concentrated to dryness under a stream of nitrogen
2. dissolutionThe residue was dissolved in 3 mL of methanol
3. additionOne drop of TFA was added to the solution
4. customthe sample was split into 3 equal volumes
5. custompurified by reverse phase preparative HPLC on a Phenx Luna Axia Column 5u (21.2×100 mm) Solvent A (10% MeOH, 90% water, 0.1% TFA), Solvent B (90% MeOH, 10% water, 0.1% TFA) 10-80% solvent B gradient, 20 mL/min, 220 nM UV detection