抗癌药物丙卡巴肼的合成工艺优化研究

Optimization of the synthetic process of antineoplastic drug procarbazine

目的对丙卡巴肼的合成工艺进行优化。方法以对甲苯甲酸为起始原料,经氯化亚砜回流得酰氯产物,再与异丙胺反应得N-异丙基对甲苯甲酰胺(3),化合物3经N-溴代丁二酰亚胺(NBS)溴代生成化合物4;甲基肼的硫酸盐在甲酸作用下生成中间体5;4与5反应得到抗癌药物丙卡巴肼。结果与结论优化了丙卡巴肼的合成工艺,以5步反应、总收率45.9%、单步收率75%～90%合成目标化合物。所有化合物的结构均经1H-NMR、13C-NMR和MS确证。

Optimization of the synthetic process of procarbazine has been conducted. Firstly, N-isopropyl-4- methylbenzamide （ 3 ） was synthesized from p-toluic acid by reaction with thionyl chloride, followed by ami- dation with isopropylamine. 3 was then transformed into N-isopropyl-4-bromomethylbenzamide （4） by bro- marion under light using N-bromosuccimide（NBS）. After changing methylhydrazine into N,N＇-diformylm- ethylhydrazine（5 ） ,procarbazine was prepared from 4 and 5 in the presence of K2CO3. The process includes 5 steps with an overall yield of 45.9%, in which the yield for each step lies between 75% to 90%. The structures of all the products were confirmed by 1H-NMR, 13 C-NMR and mass spectroscopy （MS） respec- tively.