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A facile and general synthesis of 2,4‐Di‐ and 2,4,7‐trisubstituted thieno[2,3‐ c ]pyridines
Author(s) -
Zhu GuiDong,
Gunawardana Indrani W.,
Boyd Steven A.,
Melcher Laura M.
Publication year - 2008
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570450106
Subject(s) - chemistry , stille reaction , pyridine , amination , decarboxylation , medicinal chemistry , saponification , bromide , deprotonation , carboxylate , halogenation , organic chemistry , catalysis , ion
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 POBr 3 , 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.