Polyfluoroalkylated antipyrines in Pd-catalyzed transformations

Evgeny V Shchegolkov; Yanina V Burgart; Daria A Matsneva; Sophia S Borisevich; Renata A Kadyrova; Iana R Orshanskaya; Vladimir V Zarubaev; Victor I Saloutin

doi:10.1039/d1ra06967e

Polyfluoroalkylated antipyrines in Pd-catalyzed transformations

RSC Adv. 2021 Oct 31;11(56):35174-35181. doi: 10.1039/d1ra06967e. eCollection 2021 Oct 28.

Authors

Evgeny V Shchegolkov¹, Yanina V Burgart¹, Daria A Matsneva¹, Sophia S Borisevich², Renata A Kadyrova³, Iana R Orshanskaya³, Vladimir V Zarubaev³, Victor I Saloutin¹

Affiliations

¹ Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences S. Kovalevskoi St., 22 Ekaterinburg 620990 Russia saloutin@ios.uran.ru.
² Ufa Institute of Chemistry, Russian Academy of Sciences 71 October Ave. Ufa 450054 Russia.
³ Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology 14 Mira St. Saint-Petersburg 197101 Russia.

Abstract

In the direct C-H arylation with arylhalogenides in the presence of Pd(OAc)₂, trifluoromethyl-containing antipyrine reacts very slowly and incompletely owing to the low nucleophilicity of its C4 center. However, it was effective in modifying polyfluoroalkyl-substituted 4-bromo- and 4-iodo antipyrines by the Suzuki and Sonogashira reactions. It was established that using Pd₂(dba)₃ as catalyst and XPhos as phosphine ligand was the optimal catalytic system for the synthesis of 4-aryl- and 4-phenylethynyl-3-polyfluoroalkyl-antipyrines. Moreover, iodo-derivatives as the initial reagents were found to be more advantageous compared to bromo-containing analogs. It was found that 4-phenylethynyl-5-CF₃-antipyrine has a moderate activity against the influenza virus A/Puerto Rico/8/34 (H1N1) and 4-iodo-5-CF₃-antipyrine reveals a weak activity against the vaccine virus (strain Copenhagen) and bovine diarrhea virus (strain VC-1).