Введення гем-дифлуороциклоалкільних замісників у гетероцикли через стратегію «видалення Нітрогену» Левіна

A series of compounds containing heterocyclic cores and gem-difluorocycloalkyl substituents was obtained under conditions of the parallel synthesis (i.e., simultaneous performance of reaction procedures, treatment of the reaction mixture, and product isolation for a number of similar transformations...

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Bibliographic Details
Date:2023
Main Authors: Holovach, Serhii M., Melnykov, Kostiantyn P., Poluektova, Maryna S., Rozhenko, Oleksandr B., Grygorenko, Oleksandr O.
Format: Article
Language:English
Published: National University of Pharmacy 2023
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Online Access:https://ophcj.nuph.edu.ua/article/view/278321
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Journal Title:Journal of Organic and Pharmaceutical Chemistry

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Journal of Organic and Pharmaceutical Chemistry
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Summary:A series of compounds containing heterocyclic cores and gem-difluorocycloalkyl substituents was obtained under conditions of the parallel synthesis (i.e., simultaneous performance of reaction procedures, treatment of the reaction mixture, and product isolation for a number of similar transformations) using the reductive amination – the “Nitrogen deletion” reaction sequence. The synthesis of the target compounds commenced from heteroaromatic aldehydes and the corresponding gem-difluorocycloalkyl or (gem-difluorocycloalkyl)methyl amines and included the NaBH3CN-mediated reductive amination and “Nitrogen deletion” upon the action of Levin’s anomeric amide. It has been shown that the method can be used to obtain compounds with the aforementioned structural fragments separated by one or two methylene units. The developed protocol allowed for the preparation of a 12-member compound library (67 % synthetic efficiency). Therefore, this novel synthetic methodology is suitable for decorating heterocyclic cores with sp3-enriched substituents that are attractive for medicinal chemistry.