A facile and general synthesis of 2,4-Di- and 2,4,7-trisubstituted thieno[2,3-c]pyridines

• Published in: Journal of heterocyclic chemistry Vol. 45; no. 1; pp. 91 - 96
• Main Authors: Zhu, Gui-Dong, Gunawardana, Indrani W., Boyd, Steven A., Melcher, Laura M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley-Blackwell 01-01-2008; Wiley‐Blackwell
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.5570450106

Treatment of 3,5‐dibromo‐ or 3,5‐dichloro‐pyridine‐4‐carboxaldehyde 2 with one equivalent of methyl thioglycolate, followed by exposure to base, provided 4‐bromo‐ or 4‐chloro‐thieno[2,3‐c]pyridine‐2‐carboxylate 4 in good yields. Oxidation of the thieno[2,3‐c]pyridine scaffold such as 7 with mCPBA, followed by treatment with POBr3, introduced a bromine exclusively at the 7‐position of the heterocycle. The 4‐ or 7‐bromide of the thienopyridines readily underwent Suzuki, Stille coupling, and Buchwald amination reactions, to afford 4‐ or 7‐substituted analogs 6 or 11. The 2‐carboxylate of 4b or 12 was smoothly removed through saponification and decarboxylation to furnish 15 or 16. Deprotonation of the thienopyridine at C‐2 position, followed by trapping with trimethyltin chloride, afforded a 2‐stannyl analog, which was readily converted to other C‐2 derivatives via Stille reaction.