Wippert Nicolai, Nieger Martin, Herlan Claudine, Jung Nicole, Bräse Stefan
Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology, Campus North, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
Department of Chemistry, University of Helsinki, P.O. Box 55 (A. I. Virtasen aukio 1), 00014 University of Helsinki, Finland.
Beilstein J Org Chem. 2021 Nov 22;17:2773-2780. doi: 10.3762/bjoc.17.187. eCollection 2021.
We describe the synthesis of so far synthetically not accessible 3,6-substituted-4,6-dihydro-3-pyrazolo[3,4-][1,2,3]triazines as nitrogen-rich heterocycles. The target compounds were obtained in five steps, including an amidation and a cyclative cleavage reaction as key reaction steps. The introduction of two side chains allowed a variation of the pyrazolo[3,4-][1,2,3]triazine core with commercially available building blocks, enabling the extension of the protocol to gain other derivatives straightforwardly. Attempts to synthesize 3,7-substituted-4,7-dihydro-3-pyrazolo[3,4-][1,2,3]triazines, the regioisomers of the successfully gained 3,6-substituted 4,6-dihydro-3-pyrazolo[3,4-][1,2,3]triazines, were not successful under similar conditions due to the higher stability of the triazene functionality in the regioisomeric precursors and thus, the failure of the removal of the protective group.
我们描述了迄今为止合成上难以获得的3,6-取代-4,6-二氢-3-吡唑并[3,4-][1,2,3]三嗪作为富氮杂环的合成方法。目标化合物通过五步反应得到，其中酰胺化反应和环化裂解反应为关键反应步骤。引入两个侧链使得可以用市售的结构单元对吡唑并[3,4-][1,2,3]三嗪核心进行修饰，从而能够扩展该方法以直接获得其他衍生物。在类似条件下，尝试合成3,7-取代-4,7-二氢-3-吡唑并[3,4-][1,2,3]三嗪（成功获得的3,6-取代-4,6-二氢-3-吡唑并[3,4-][1,2,3]三嗪的区域异构体）未成功，这是由于区域异构体前体中三氮烯官能团的稳定性较高，因此保护基团无法去除。
