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The synthesis of symmetrical (2‐indolyl)ethynes and reduced congeners via palladium‐catalyzed couplings of 2‐bromoindole precursors
Author(s) -
Sercel Anthony D.,
Hollis Showalter H. D.
Publication year - 2006
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.5570430326
Subject(s) - chemistry , palladium , sonogashira coupling , acetylene , stille reaction , aldehyde , amide , catalysis , stereochemistry , trimethylsilyl , linker , ethylene , syk , medicinal chemistry , combinatorial chemistry , organic chemistry , tyrosine kinase , receptor , biochemistry , computer science , operating system
tarting from a series of 2‐bromo‐1‐methylindole precursors ( 1b‐e ) activated in the 3‐position with aldehyde, ester, or amide functionality, two approaches have been developed toward the synthesis of 2,2′‐bis(indolyl)ethynes and reduced congeners via palladium(0)‐ or palladium(II)‐catalyzed couplings. The first approach utilized Sonogashira coupling of (trimethylsilyl)acetylene to introduce the two‐carbon linker followed by desilylation and further coupling with starting 2‐bromoindole. A second shorter and more efficient route engaged the starting 2‐bromoindole in a double Stille coupling with bis(tributylstannyl) acetylene or ( E )‐1,2‐bis(tributylstannyl)ethylene to provide desired homodimers in one step. Subsequent transformations of dimeric intermediates led to target acids 7a‐c and derived amides 8a‐c and 9 . When tested against a panel of tyrosine kinases, each target compound was found to be inactive.