新型抗癌药物尼洛替尼的合成工艺研究  

The synthesis of the new anticancer drugs Nilotinib

作　　者：高朔漠 刘毅锋[1] 张娟[1] 殷玉英[1] 

机构地区：[1]西北大学应用化学研究所,陕西西安710069

出　　处：《西北大学学报（自然科学版）》2015年第4期590-594,共5页Journal of Northwest University（Natural Science Edition）

基　　金：陕西省教育厅产业化培育基金资助项目(2011JG03)

摘　　要：研究尼洛替尼的合成工艺及方法。以O-甲基异脲硝酸盐为原料,与3-氨基-4-甲基苯甲酸酯在醇类溶剂中反应得到3-胍基4-甲基苯甲酸酯硝酸盐,然后再和3-(二甲基氨基)-1-(3-吡啶基)-2-丙烯-1-酮环化生成嘧啶胺衍生物。在金属有机化合物存在下,中间体和3-氨基-5-溴三氟甲苯发生胺解反应得到,最后,再和4-甲基咪唑进行碳氮偶联反应得到尼洛替尼。通过1H NMR,IR和元素分析,表征了目标产物的结构,与尼洛替尼一致。该合成方法路线简捷、绿色环保、成本低、反应条件较温和。To study on the synthetic method of Nilotinib. The reaction of O-methylisourea nitrate as raw materi- als, with methyl 3-amino-4-methylbenzoate in an alcoholic solvent to afford 3-guanidino-4-methylbenzoate ni- trate, and then, the cyclization reaction of intermediate with 3-（dimethylamino） -1-（3-pyridyl） -2-propen-1- one gave a pyrimidine amine derivative. In the presence of metal organic compound, the aminolysis reaction of intermediates with 3-amino-5-bromobenzotrifluoride occured. Finally, Nilotinib was synthetised by the carbon and nitrogen coupling reaction of with 4-methyl imidazole. By 1H NMR, IR and elemental analysis, the struc- ture of target product was characterized, consistent with the results of Nilotinib. This method is simple with milder reaction conditions, low cost, and is environmental friendly.

关 键 词：O-甲基异脲硝酸盐 3-氨基-5-溴三氟甲苯 3.氨基-4-甲基苯甲酸甲酯 胍 尼洛替尼 

分 类 号：O62[理学—有机化学]