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Updated: Jun 9, 2025

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Functional Hexafluoroisopropyl Group Used in the Construction of Biologically Important Pyrimidine Derivatives
Shuo Yuan1,2, Xiang Li3, Yue-Lin Zhang3
1Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450018, China.
Abstract:
A series of versatile 4-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)pyridine intermediates have been developed to efficiently produce biaryls, amines, ethers, and thioethers. These hydrolysis-stable ether intermediates exhibit reactivity toward electron-donating groups and nucleophiles in cross-coupling and nucleophilic substitution reactions while surpassing the stability of corresponding aryl halides. In comparison to conventional coupling methods, this protocol offers an alternative pathway for accessing natural product and drug-like compounds without the need for metal catalysts. With assistance of this approach, we successfully obtained a potent P-glycoprotein inhibitor 4k (YS-370), a potent epidermal growth factor receptor inhibitor 4l (YS-363), and a promising lysine-specific demethylase 1 inhibitor 5g.
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