Application of 2-Aminopyridines in the Synthesis of Five- and Six-Membered Azaheterocycles

Abstract

2-Aminopyridine is a significant synthetic synthon, with unique dual nucleophilic structure. It can react with ketones, aldehydes, acids, multifunctional esters, halogenated aromatics and other compounds to synthesize five-and six-member azaheterocycles. In recent years, the cyclization reactions based on 2-aminopyridines have been under the spotlight. According to the different types of substrates, the research progress on the synthesis of imidazo[1,2-a]pyridines and pyrido[1,2-a]pyrimidines based on 2-aminopyridines in the past 5 years is reviewed, and its applications in organic synthesis methodology, drug synthesis and fluorescent probes are summarized. Furthermore, the development trend of green cyclization and its application based on 2-aminopyridines in the future are prospected. Keywords 2-aminopyridine; imidazo[1,2-a]pyridine; pyrido[1,2-a]pyrimidine; azaheterocycle; C-N bond formation; retrosynthetic analysis 吡啶环上氮原子具有较强的吸电子效应, 且吡啶 α 位基团具有特殊的作用, 使吡啶 α 位的衍生物作为合成 子或中间体在有机合成、药物合成中日益引人瞩目 [1][2][3] . 其中, 2-氨基吡啶作为最典型的一种, 因其独特的双亲 核结构特点为人们所重视 [4] , 特别是基于吡啶环上的氮 与氨基的成环反应倍受关注 [5][6][7] .