A study of the reaction route of 1,3-diphenyl-1H-pyrazol-5-amine with N-(4-fluorophenyl)itaconimide by HPLC-MS
Abstract
The modern rational design of the structure of organic compounds needs to be highly efficient to allow both increasing molecular complexity and minimising the number of steps in synthetic procedures. These problems are even more relevant when designing various polyazaheterocyclic matrices, including those with a pyrazolopyridine backbone, which is one of the common fragments in the structures of natural and synthetic biologically active compounds. The preparation of new polysubstituted heterocyclic compounds is a complex multi-step process involving both consecutive and parallel steps that complicate the control of the reactions and product separation. In addition, the main problem associated with the study of cascade reactions using various polynucleophilic reagents is to determine the order of processes leading to the target products. Therefore, the problems associated with the study of the mechanisms of the formation of heterocyclic systems and the identification of intermediates, whose individualisation is very difficult, are relevant.
Currently, mass spectrometry is a selective, highly sensitive, and rapid method for determining different types of compounds in multi-component samples. This allows using high-performance liquid chromatography in combination with mass spectrometry (HPLC/MS) to study routes of complex reactions to identify their products and intermediates. Unlike the widely used TLC method, HPLC/MS makes it possible to preliminarily estimate the components of the reaction mass from mass spectrometry data.
The purpose of this study is to develop an effective method for controlling the synthetic process between N-(4-fluorophenyl)itaconimide 1 and 1,3-diphenyl-1H-pyrazol-5-amine 2 to identify the final products and possible intermediates. The reaction with the reactants was carried out when boiled for several hours in isopropyl alcohol in the presence of catalytic amounts of acetic acid. Samples for chromatography were taken from the reaction mass at specified intervals. Interpretation of the chromatographic analysis results revealed that in addition to the expected N-(4-fluorophenyl)-2-(6-oxo-1,3-diphenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-5-yl)acetamide 5, 7-(4-fluorophenyl)-1,3-diphenyl-4,4a,5,7-tetrahydropyrazolo[3,4-b]pyrrolo[3,2-e] pyridin-6(1H)-one 6 was formed during the reaction. It was shown that the reaction mass had two minor components, which were obviously intermediates.
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References
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