13472-79-2Relevant articles and documents
A highly efficient Suzuki-Miyaura methylation of pyridines leading to the drug pirfenidone and its CD3 version (SD-560)
Falb, Eliezer,Ulanenko, Konstantin,Tor, Andrey,Gottesfeld, Ronen,Weitman, Michal,Afri, Michal,Gottlieb, Hugo,Hassner, Alfred
supporting information, p. 5046 - 5053 (2017/11/09)
Efficient introduction of methyl or methyl-d3 into aromatic and heteroaromatic systems still presents a synthetic challenge. In particular, we were in search of a non-cryogenic synthesis of the 5-CD3 version of pirfenidone (4d, also known as Pirespa, Esbriet or Pirfenex), one of the two drugs approved to date for retarding idiopathic pulmonary fibrosis (IPF), a serious, rare and fatal lung disease, with a life expectancy of 3-5 years. The methyl-deuterated version of pirfenidone (4e, also known as SD-560) was designed with the objective of attenuating the rate of drug metabolism, and our goal was to find a green methylation route to avoid the environmental and economic impact of employing alkyllithium at cryogenic temperatures. The examination of several cross-coupling strategies for the introduction of methyl or methyl-d3 into methoxypyridine and pyridone systems culminated in two green and nearly quantitative Suzuki-Miyaura cross-coupling routes in the presence of RuPhos ligand: the first, using commercially available methyl boronic acid or its CD3 analog and the second, employing potassium methyl trifluoroborate or CD3BF3K, the latter obtained by a new route in 88% yield. This led, on a scale of tens of grams, to the synthesis of pirfenidone (4d) and its d3 analog, SD-560 (4e), at 99% isotopic purity.
Environmental friendly method for the iodination of moderately active arenes
Sathiyapriya
experimental part, p. 41 - 43 (2011/11/13)
An effective and environmental friendly method for the iodination of various moderately active methoxy arenes, phenols and anilines using hydrogen peroxide and acidified sodium periodate in aqueous ethanol medium is reported. The extent of iodination is e
An Efficient and Selective Method for the Preparation of Iodophenols
Edgar, Kevin J.,Falling, Stephen N.
, p. 5287 - 5291 (2007/10/02)
Direct iodination of a wide range of phenols may be achieved with unprecedented selectivity in aqueous alcohol solvents by the action of a reagent preparated in situ from sodium hypochlorite and sodium iodide.Para-substituted phenols (or ortho-substituted, when the para-position is already occupied) are obtained in fair to excellent yields by simple isolation techniques.The extent of iodination is easily controlled by stoichiometry.The technique is also useful with some anilines.
