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Synthesis 2023; 55(21): 3526-3534
DOI: 10.1055/s-0041-1738433
special topic
C–H Bond Functionalization of Heterocycles

Palladium-Catalyzed C7–H (Hetero)arylation of Pyrazolo[1,5-a]pyrazines with Heteroarenes and Aryl Iodides with the Assistance of Silver Salts

Thanh V. Q. Nguyen  ∗
a   Medicinal Chemistry, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
,
Armand Levoin
a   Medicinal Chemistry, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
b   University of Strasbourg, 4 Rue Blaise Pascal, 67081 Strasbourg, France
,
Lorenzo Poli
a   Medicinal Chemistry, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
b   University of Strasbourg, 4 Rue Blaise Pascal, 67081 Strasbourg, France
› Author AffiliationsL.P. and A.L. are grateful to Erasmus and Grand Est (Alsace region) for financial support during their internship stay at AstraZeneca (AZ).
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Abstract

Pyrazolo[1,5-a]pyrazines coupled with heteroarenes and aryl iodides selectively at the C7 position to afford a broad library of bi(hetero)aryl structures under ligand-free palladium-catalyzed conditions. The key to the success of the reaction is the use of silver salts as the oxidant or the base, allowing the regioselective C–H bond functionalization to occur under relatively mild conditions.

Key words

C–H bond functionalization - fused-ring systems - heteroarenes - homogeneous catalysis - synthetic methods

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0041-1738433.
  • Supporting Information


Publication History

Received: 13 December 2022

Accepted after revision: 30 January 2023

Article published online:
06 March 2023

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