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Synthetic entries to 6‐fluoro‐7‐substituted indole derivatives
Author(s) -
Mckittrick Brian,
Failli Amedeo,
Steffan Robert J.,
Soll Richard M.,
Hughes Philip,
Schmid Jean,
Asselin Andre A.,
Shaw C. C.,
Noureldin R.,
Gavin G.
Publication year - 1990
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.5570270755
Subject(s) - chemistry , indole test , metalation , nucleophile , stereochemistry , combinatorial chemistry , organic chemistry , catalysis
Three practical synthetic entries of functionalized 6‐fluoro‐7‐substituted indole derivatives were developed in connection with the preparation of 7‐fluoro‐8‐substituted‐1,3,4,9‐tetrahydropyrano[3,4‐ b ]indole‐1‐acetic acid derivatives 11 . The first route, which permits group modification about position 8 of the pyranoindole skeleton, employs 2‐bromo‐3‐fluoroaniline ( 18 ) as a key intermediate, the preparation of which was achieved by either a novel ortho metalation of 15 or via the intermediacy of 22 . The second route utilizes 32 to append a terminally functionalized three carbon side chain onto the indole template and in addition leads to 43 from 40 . The third route to the 7‐fluoro‐8‐substituted‐pyranoindole skeleton complements route two in that the synthetic pathway exploits 32 in a nucleophilic fashion to construct a terminally functionalized two carbon appendage onto the indole nucleus.