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

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.