5-芳基-7-三氟甲基吡唑并[1,5-a]嘧啶类化合物的合成  

Synthesis of 5-Arylsubstituted-7-Trifluoromethyl Pyrazolo[1,5-a] pyrimidines

作　　者：徐利锋[1] 石磊[2] 刘举[1] 敬春燕[1] 滕鹏飞[1] 徐嘉瞳[1] 王洋[1] 刘凤芝[2] 

机构地区：[1]辽宁大学药学院,辽宁沈阳110036 [2]哈尔滨医科大学药学院,黑龙江哈尔滨150081

出　　处：《辽宁大学学报（自然科学版）》2013年第1期76-80,共4页Journal of Liaoning University：Natural Sciences Edition

基　　金：国家十二五"重大新药创制"科技重大专项(2011ZX09102-007-02)

摘　　要：吡唑并[1,5-a]嘧啶类化合物与嘌呤结构非常类似.大量研究表明这类化合物具有广泛的生物活性及药理活性.实验合成了三个7-三氟甲基-5-芳基吡唑并[1,5-a]嘧啶类化合物(5a,5b和7).乙氧基甲叉基氰乙酸乙酯(1)与水合肼在乙醇中回流反应制备了中间体5-氨基-1H-吡唑-4-羧酸乙酯(2);取代苯乙酮(3)与三氟乙酸乙酯缩合反应得到1-取代苯基-4,4,4-三氟丁二酮(4);然后,化合物2与化合物4在乙酸回流条件下反应得到5-(4-取代苯基)-7-三氟甲基吡唑并[1,5-a]嘧啶-3-羧酸乙酯(5a,5b),5a经过NBS溴代、最后溴代中间体与吗啉反应制备目标产物7.其结构经核磁共振氢谱和红外光谱进行了表征.Pyrazolo[4,5-a]pyrimidines have shown many excellent biological activities in the areas of medicine.In this paper,three novel trifluoromethylated pyrazolopyrimidines(5a,5b and 7) were synthesized.The intermediate ethyl 5-amino-1H-pyrazole-4-carboxylate(2) was prepared via the condensation of ethyl 2-cyano-3-ethoxyacrylate and hydrazine hydrate.4,4,4-trifluoro-1-(4-substitutedphenyl)butane-1,3-dione(4) were obtained by the reaction of acetophenone with ethyl trifluoroacetate.The desired pyrazolopyrimidines(5a,5b) were prepared via the condensation of ethyl 5-amino-1H-pyrazole-4-carboxylate(2) and 4,4,4-trifluoro-1-(4-substitutedphenyl)butane-1,3-dione(4) in good yields.The compound 7 was obtained by the reaction of 5a with NBS,and then reacted with morpholine in N,N-dimethylformamide.The structure were characterized by IR and 1HNMR.

关 键 词：吡唑并[1 5-a]嘧啶 生物活性 三氟甲基 合成 

分 类 号：R914.2[医药卫生—药物化学] O626.23[医药卫生—药学]