抗癌药物丙卡巴肼的合成工艺再优化  

Re-optimization of the synthetic process for antineoplastic drug procarbazine

作　　者：潘龙[1] 汪亚帷 刘笑天 陈河如[1,2] 

机构地区：[1]暨南大学药学院中药及天然药物研究所,广东广州510632 [2]广东省中药药效物质基础及创新药物研究重点实验室,广东广州510632

出　　处：《暨南大学学报（自然科学与医学版）》2015年第1期7-10,共4页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：国家自然科学基金项目(81172982)

摘　　要：以对甲基苯甲酸为起始原料，与氯化亚砜反应得对甲基苯甲酰氯（2），酰氯直接与异丙胺反应得对甲苯甲酰异丙胺（3）；化合物3经硝酸铈铵（CAN）氧化得4-甲酰基苯甲酰异丙胺（4）；以氰基硼氢化钠为还原剂，化合物4与甲基肼硫酸盐在碱性条件下经经缩合还原反应生成目标化合物丙卡巴肼．该工艺路线共4步反应，总收率44.7％，每个单元反应收率71％～86％．所有化合物的结构均经1 H-NMR、13 C-NMR 和 MS 确认．Procarbazine has been prepared through a four-steps process.Firstly,4-methylbenzoyl chloride was synthesized by reaction of 4-methylbenzoic acid with dimethyl sulfoxide.The direct reaction of this chloride with isopropylamine form N-isopropyl-4-methylbenzamide.The amide was then oxidized to 4-formyl-N-isopropylbenzamide by using ammonium ceric nitrate as oxidant.Afterwards,this intermediate condensed with methylhydrazine sulfate and then reduced by sodium cyanoborohydride under basic condi-tion to offer the target compound.The overall yield was 44.7%.The yield of each unit reaction was 71%to 86%.All the intermediates and target product were identified by 1 H NMR,13 C NMR and mass spec-troscopy （MS）.

关 键 词：丙卡巴肼 合成工艺 药物合成 抗肿瘤 

分 类 号：O629.7[理学—有机化学]