Preparation of 5-Functionalised Pyridine Derivatives using a Br/Mg Exchange Reaction: Application to the Synthesis of an Iron-Chelator Prodrug

Abstract

A novel preparation of 5-functionalised pyridine derivatives is reported from 5-bromo-4-tosyloxypyridines via a Br/Mg exchange procedure with i-PrMgCl·LiCl, followed by addition of an electrophile. The reaction was carried out under mild conditions and gave good to high yields. The resulting 5-functionalised pyridine derivatives enrich the library of pyridinone-type iron-chelator prodrugs.

Synthesis of 5-Aroyl-2-aryl-3-hydroxypyridin-4(1H)-ones

“…3-Hydroxy-4-pyridones (3, are well-known bidentate chelation agents for many metals [1][2][3]. The first marketed drug possessing a 3,4-HPO scaffold, deferiprone (Ferriprox), is an iron chelating agent for treating thalassemia approved in 1999 (Figure 1).…”