尼洛替尼的合成研究  

Synthesis of Nilotinib

作　　者：禹艳坤[1] 王超[1] 刘爱霞[1] 冀亚飞[1] 

机构地区：[1]华东理工大学药学院,上海200237

出　　处：《化学试剂》2011年第3期266-268,共3页Chemical Reagents

摘　　要：3-乙酰基吡啶与N,N-二甲基甲酰胺二甲缩醛反应制得(E)-3-二甲胺基-1-(3-吡啶基)-2-丙烯-1-酮,接下来与硝酸胍环合得4-(3-吡啶基)-2-胺基嘧啶,然后与3-溴-4-甲基苯甲酸乙酯缩合再经水解反应制得关键中间体4-甲基-3-[[4-(3-吡啶基)-2-嘧啶基]胺基]苯甲酸。此关键中间体直接与3-三氟甲基-5-(4-甲基-1H-1-咪唑基)苯胺进行酰胺化反应,最终制得高选择性酪氨酸激酶抑制剂尼洛替尼,总收率约39.4%。3-Acetylpyridine reacted with N,N-dimethylformamide dimethyl acetal to form（E）-3-dimethylamino-1-（pyridin-3-yl）prop-2-en-1-one,which was cyclized with guanidine nitrate to obtain 4-（pyridin-3-yl）-2-aminopyrimidine.4 was condensed with ethyl 3-bromo-4-methylbenzoate followed by hydrolysis to provide the key intermediate 4-methyl-3-（4-（pyridin-3-yl）pyrimidin-2-ylamino）benzoic acid.Finally,6 was directly amidated with 3-trifluoromethyl-5-（4-methyl-1H-imidazol-1-yl）-benzenamine to achieve the highly selective inhibitor of tyrosine kinase,nilotinib with an overall yield of 39.4%.

关 键 词：尼洛替尼 酪氨酸激酶抑制剂 抗白血病药 合成 

分 类 号：TQ463.5[化学工程—制药化工]