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Modification of Pyrrolo[2,3‐ d ]pyrimidines by C–H Borylation Followed by Cross‐Coupling or Other Transformations: Synthesis of 6,8‐Disubstituted 7‐Deazapurine Bases
Author(s) -
Klečka Martin,
Poštová Slavětínská Lenka,
Hocek Michal
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201501177
Subject(s) - chemistry , borylation , pyrimidine , aryl , trifluoromethyl , amination , suzuki reaction , pinacol , coupling reaction , demethylation , combinatorial chemistry , sulfone , medicinal chemistry , stereochemistry , catalysis , organic chemistry , biochemistry , alkyl , gene expression , dna methylation , gene
A general access to 4‐substituted 6‐arylpyrrolo[2,3‐ d ]pyrimidine (6‐substituted 8‐aryl‐7‐deazapurine derivatives) was developed based on iridium‐catalyzed C–H borylations of pyrrolo[2,3‐ d ]pyrimidines at the 6‐position followed by the Suzuki cross‐coupling reactions or other functional group transformations of the boronates. Biologically relevant 6‐arylpyrrolo[2,3‐ d ]pyrimidin‐4‐amines (8‐aryl‐7‐deazaadenines) and pyrrolo[2,3‐ d ]pyrimidin‐4‐ones (–7‐deazahypoxanthines) were synthesized starting from SEM‐protected 4‐methylsulfanyl‐ or 4‐methoxypyrrolo[2,3‐ d ]pyrimidine. The one‐pot borylation/Suzuki coupling reactions were followed either by demethylation and deprotection to yield deazahypoxanthine bases, or by oxidation of sulfide to sulfone, amination and deprotection to give deazaadenines. In addition, the boronate intermediates were converted into 6‐halo‐ or 6‐(trifluoromethyl)pyrrolo[2,3‐ d ]pyrimidine (8‐halo‐ or 8‐trifluoromethyl‐7‐deazapurine) derivatives.