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Synthesis of imidazo[4,5‐ c ]pyridines with a trifluoromethyl group at C‐4 and/or C‐6
Author(s) -
Gautam Rakesh K.,
Fujii Shozo,
Nishida Masakazu,
Kimoto Hiroshi,
Cohen Louis A.
Publication year - 1994
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.5570310235
Subject(s) - chemistry , trifluoromethyl , group (periodic table) , stereochemistry , medicinal chemistry , organic chemistry , alkyl
Thermal condensation of histamine with trifluoroacetaldehyde gives 4‐(trifluoromethyl)spinacamine and subsequent dehydrogenation with selenium dioxide leads to 4‐(trifluoromethyl)‐1 H ‐imidazo[4,5‐ c ]pyridine (42%). Fluorination with sulfur tetrafluoride of L‐spinacine, obtained from the condensation of L‐histidine with formaldehyde, affords 6‐(trifluoromethyl)spinacamine, which can be converted to 6‐(trifluoromethyl)‐1 H ‐imidazo[4,5‐ c ]pyridine with selenium dioxide (49%). Application of the sequential reactions to 4‐(trifluoro‐methyl)‐L‐spinacine gives 4,6‐bis(trifluoromethyl)‐1 H ‐imidazo[4,5‐ c ]pyridine. Dehydrogenation of the tetrahydropyridine ring also occurred during the fluorination with sulfur tetrafluoride.