Synthesis of new thieno[3,2-b]pyridine derivatives by palladium-catalyzed couplings and intramolecular cyclizations

Two methyl 3-aminothieno[3,2-b]pyridine-2-carboxylates were prepared from 3-fluoro or 3-nitropicolinonitriles and methyl thioglycolate in DMF/KOH(aq). From the unsubstituted precursor in the pyridine ring, di(hetero)arylamines were obtained by C–N Buchwald–Hartwig coupling with bromonitrobenzenes and with 2-bromopyridine. In the latter case a tetracyclic compound was formed by intramolecular cyclization. Using a brominated derivative in the pyridine ring as a coupling component, it was possible to synthesize C–C (Suzuki and Sonogashira) and C–N (Buchwald–Hartwig) coupling products and a tetracyclic compound obtained by bifunctionalization of the thienopyridine system.