A sustainable and scalable multicomponent continuous flow process to access fused imidazoheterocycle pharmacophores
A sustainable and scalable multicomponent continuous flow process to access fused imidazoheterocycle pharmacophores
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DOI：
10.1039/d0gc03675g
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发表时间：
2021-01-07
期刊：
影响因子：
9.8
通讯作者：
Poole, Darren L.
中科院分区：
文献类型：
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作者：
Baker, Blake J. M.;Kerr, William J.;Poole, Darren L.
本文描述了通过Groebke-Blackburn-Bienayme反应（GBBR）合成各种氨基咪唑并杂环的绿色连续流方法。这种多组分的程序结合氨基嗪，醛和异腈，以产生各种各样的医药特权，胺化咪唑杂环架构。该方法在乙醇中进行，仅使用无机酸而不是该领域典型的标准金属基催化剂。这些可持续性的好处已被证明，甚至在多克规模，例证了该程序的简易可扩展性。与目前可用的方法相比，该方法还具有更短的反应时间，更宽的范围鲁棒性和更高的产率，不需要水性后处理程序，从而为一系列具有学术和工业兴趣的医学目标提供具有显著相关性的所得支架。
Described herein is a green, continuous flow process for the synthesis of various aminoimidazoheterocycles, through the Groebke-Blackburn-Bienayme reaction (GBBR). This multicomponent procedure combines aminoazines, aldehydes and isocyanides to generate a wide variety of medicinally privileged, aminated imidazoheterocycle architectures. This method is performed in ethanol, using only mineral acid rather than the standard metal-based catalysts typical to the field. These sustainability benefits have been demonstrated even on multigram scale, exemplifying the facile scalability of the procedure. The process also boasts shorter reaction times, wider scope robustness, and improved yields compared to the currently available methods, with no requirement for an aqueous work-up procedure, affording resulting scaffolds of notable relevance, to a range of medicinal targets of academic and industrial interest.