4-[[4-氟-3-(4-丙基哌嗪-1-羰基)苄基]甲基]-2H-酞嗪-1-酮合成工艺研究

Synthesis of 4-[[4-Fluoro-3-(4-propylpiperazine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one

目的:对PARP抑制剂4-[[4-氟-3-(4-丙基哌嗪-1-羰基)苄基]甲基]-2H-酞嗪-1-酮的合成工艺进行了改进。方法:使用更为价廉的邻苯二甲酰亚胺作为起始原料,经选择性还原、加成、水解制得关键中间体2-氟-5-[(4-氧代-3,4-二氢酞嗪-1-基)甲基]苯甲酸,然后与1-叔丁氧羰基哌嗪缩合,卤代烃取代制得目标化合物。结果:用质谱、核磁共振氢谱确定了目标化合物的结构,总收率达30.4%。结论:与原工艺相比,该方法起始原料价廉易得,降低了成本,避免了大量的含碱废水,减少了环境污染。

The synthesis of the PARP Inhibitors4-（4-fluoro-3-（piperazine-1-carbonyl）benzyt）phthalazin-l（2H）-one was optimized. The key intermediate was prepared with Phthalimideas the starting material, by reduction, addition reaction, hydrolysis and 2-fluoro-5-[（4-oxo-3h-phthalazin-l-yl）methyl]Benzoie acid was obtained, and then the target compound was synthesized by the condensation of tert-butyl piperazine- 1-carboxylate with the key intermediate mentioned above, after substitution by halogenated hydrocarbons. The total yield was 30.4%. Structures of the target product and key intermediates were verified by MS and IHNMR.Compared with the original process, The optimal synthetic procedure with lower cost avoided the generation of a large amount of alkali-containing wastewater and reduced environmental pollution.