反应详情

温度

100 °C

To a solution of 3-iodo-1-[2-(4-methylpiperazin-1-yl)ethyl]-5-phenyl-pyrazolo[3,4-c]pyridazin-4-ol (120 mg, 0.26 mmol) in dioxane (1.7 mL) and DMSO (0.9 mL) was added pyrrolidine (233 μL, 2.8 mmol) and sodium t-butoxide (37 mg, 0.39 mmol) and nitrogen was bubbled in the resulting mixture for 30 min. Pd2dba3 (24 mg, 0.026 mmol) and Xantphos (9 mg, 0.016 mmol) were then added, the tube flushed with nitrogen, sealed and heated to 100° C. for 5 h. Pyrrolidine (40 μL, 0.49 mmol), Pd2dba3 (24 mg, 0.026 mmol) and Xantphos (9 mg, 0.016 mmol) were added and the mixture was heated to 100° C. for another 1 h. The mixture was left to cool to rt, then neutralised to pH 2-3 before loading on an SCX (10 g) cartridge. The cartridge was eluted with MeOH then CH2Cl2/MeOH (1:1) and finally the product was released with 10% methanolic ammonia (7 N) in CH2Cl2/MeOH (1:1). Evaporation of the solvent gave the title compound as a yellow glass (94 mg) which was reacted as such in the next step.

1. customwas bubbled in the resulting mixture for 30 min
2. customthe tube flushed with nitrogen
3. customsealed
4. temperaturethe mixture was heated to 100° C. for another 1 h
5. waitThe mixture was left
6. temperatureto cool to rt
7. washThe cartridge was eluted with MeOH
8. customEvaporation of the solvent