Title:Regioselective Synthesis of Cycloalkane-fused Pyrazolo[4,3-e]pyridines through Tandem Reaction of 5-aminopyrazoles, Cyclic Ketones and Electron-rich Olefins
Volume: 21
Issue: 7
Author(s): Paola Cuervo-Prado*, Fabián Orozco-López, Christian Becerra-Rivas, Diego Leon-Vargas, John Lozano-Oviedo and Justo Cobo
Affiliation:
- Department of Chemistry, Group of Studies on Synthesis and Applications of Heterocyclic Compounds, Universidad Nacional de Colombia, Bogotá, Colombia, AA, 14490
Keywords:
Pyrazolopyridines, electron-rich olefins, microwave, tandem reaction, regioselectivity, pyrazole ring.
Abstract:
Background: Pyrazolopyridines are interesting fused heterocyclic pharmacophores
that combine pyrazole and pyridine; two privileged nuclei extensively studied and with a wide
range of applications. They can be obtained by a broad variety of synthetic methods among
which multicomponent reactions have gained importance, especially from 5-aminopyrazoles and
dielectrophilic reagents. However, the search for new approaches more in tune with sustainable
chemistry and the use of unconventional heating in three-component synthesis are open and
highly relevant study fields.
Methods: A novel, practical and efficient three-component synthesis of cycloalkane-fused pyrazolo[
4,3-e]pyridines was developed through a tandem reaction of 5-aminopyrazoles, cyclic ketones
and electron-rich olefins, using microwave induction in perfluorinated solvent and iodine
as catalyst.
Results: The microwave-induced three-component approach applied in this work promoted the
construction of 10 new pyrazolopyridines with high speed and excellent control of regioselectivity,
favoring the linear product with good yields; where the versatility of electron-rich olefins
in iodine-catalyzed cascade heterocyclizations, granted the additional benefit of easy isolation
and the possibility to reuse the fluorous phase.
Conclusion: Although pyrazolopyridines have been synthetically explored because of their
structural and biological properties, most of the reported synthetic methods use common or even
toxic organic solvents and conventional heating or multi-step processes. In contrast, this study
applied a multicomponent methodology in a single step by microwave induction and with the
versatility provided in this case by the use of perfluorinated solvent, which allowed easy isolation
of the final product and recovery of the fluorous phase.
