Synthesis of 2-(hetero)arylthieno[2,3-b] or [3,2-b]pyridines from 2,3-dihalopyr...

• Author(s): Peixoto, Daniela ; Begouin, Agathe ; Queiroz, Maria João R. P.
• Date: 2012
• Persistent ID: http://hdl.handle.net/1822/22010
• Origin: RepositóriUM - Universidade do Minho
• Subject(s): Thienopyridines; Sodium sulfide; Sonogashira coupling; Intramolecular cyclization; Halogenation; 1,3-Diarylureas
• Document Type: Article
• Language: English

Description

A simple and efficient three-step methodology is described for the first time for the synthesis of 2-(hetero)arylthieno[2,3-b] or [3,2-b]pyridines. The first step is a Sonogashira coupling from 3-bromo-2-chloropyridine or 2-bromo-3-chloropyridine with several (hetero)arylalkynes to obtain the corresponding 2- or 3-chloro(hetero)arylethynylpyridines. These were cyclized by treatment with Na2S affording the expected 2-(hetero)arylthienopyridines. As an improvement, these reactions were also performed in one-pot, without the isolation of the Sonogashira product, giving the thienopyridines in similar or better yields, reducing significantly the reaction time after the addition of Na2S. Further functionalizations were achieved in the thienopyridine system either by bromination in the thiophene ring or chlorination in the pyridine ring via a N-oxide intermediate, allowing metal-catalyzed coupling reactions and/or nucleophilic substitutions. The functionalization of some substituents is also possible and as an example a 1,3-diarylurea was obtained from the reaction of an aniline derivative with an arylisocyanate.