Regioselective Copper(I)-Catalyzed Direct C(3)-H (Hetero)arylation of 6-(Hetero)arylated 1,2,4-Triazolo[4,3- b]pyridazines: Ligand-Free Approach

J Org Chem. 2024 Dec 6;89(23):16999-17008. doi: 10.1021/acs.joc.4c00724. Epub 2024 Nov 24.

Abstract

The first efficient Cu(I) catalyzed regioselective C3-(hetero)arylation of 6-(hetero)arylated 1,2,4-triazolo[4,3-b]pyridazines has been developed to streamline the synthesis of pharmaceutically important 3,6-diarylated 1,2,4-triazolo[4,3-b]pyridazines. This direct (hetero)arylation is compatible with a range of aryl iodides and tolerates a variety of functional groups (23 examples). A series of new 3,6-diarylated 1,2,4-triazolo[4,3-b]pyridazines were synthesized with good to excellent yields (up to 98%). The reactivity varied depending on the nature of the aryl iodide and the substituent in position 6 of the starting substrate. The procedure is experimentally simple, cost-effective, and free of additional ligands and cocatalysts.