N-PROPARGYLATION AND COPPER(I)-CATALYZED AZIDE-ALKYNE CYCLOADDITION AS A CONVENIENT STRATEGY FOR DIRECTED POST-SYNTHETIC MODIFICATION OF 4-OXO-1,4-DIHYDROCINNOLINE DERIVATIVES

Abstract

4-Oxo-1,4-dihydrocinnoline derivatives as promising inhibitors of protein tyrosine phosphatase 1В were subjected to post-synthetic modification via a sequence of propargylation and copper(I)-catalyzed azide-alkyne cycloaddition reactions. The propargylation of 4-oxo-1,4-dihydrocinnolines with propargyl bromide in the presence of various bases proceeded regioselectively at the cinnolinone N-1 atom. In the cycloaddition reaction of N-propargylcinnolinones and benzyl azide, the highest catalytic activity of copper(I) N-heterocyclic carbene complex [(IMes)Cu(Br,I)] was observed, compared to [(IMes)CuCl], [(IPr)Cu(Cl,Br,I)], and CuI.

Authors: Vladimir N. Mikhaylov, Artem O. Pavlov, Yaroslav V. Ogorodnov, Dar'ya V. Spiridonova, Viktor N. Sorokoumov, Irina A. Balova*