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Streamlined Synthesis of Diaminopyridines by Pd‐Catalyzed Ammonia Coupling with Deactivated Amino‐Chloropyridines
Author(s) -
Bourriquen Florian,
BruneauVoisine Antoine,
Jeandin Aliénor,
Stihle Etienne,
Fantasia Serena
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201902147
Subject(s) - combinatorial chemistry , ammonia production , catalysis , coupling reaction , chemistry , palladium , reaction conditions , ammonia , enabling , substituent , coupling (piping) , computer science , nanotechnology , biochemical engineering , materials science , organic chemistry , engineering , metallurgy , psychology , psychotherapist
An efficient and cost‐effective two‐step synthesis of diaminopyridines, fundamental building blocks of biologically active compounds, is reported. The advantages over previously reported routes include cost and wider availability of the bromo‐chloropyridine starting materials and the straightforward accessibility to an extended array of diaminopyridine regioisomers. The key enabler of this synthetic strategy is the development of an unprecedented palladium‐catalyzed coupling reaction of ammonia with chloropyridines deactivated by the presence of an alkylamino substituent. The coupling reaction was accomplished with very low catalyst loadings under remarkably mild reaction conditions, making the system particularly suitable for both academic and industrial applications. The utility of this methodology is exemplified by the application to the synthesis of highly relevant scaffolds, including the synthetic intermediates of the marketed drugs Ribociclib and Palbociclib.