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Synthesis of Bi‐ and Polyfunctional Isoxazoles from Amino Acid Derived Halogenoximes and Active Methylene Nitriles
Author(s) -
Chalyk Bohdan A.,
Hrebeniuk Kateryna V.,
Gavrilenko Konstantin S.,
Shablykin Oleh V.,
Yanshyna Oksana O.,
Bash Daniil,
Mykhailiuk Pavel K.,
Liashuk Oleksandr S.,
Grygorenko Oleksandr O.
Publication year - 2018
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.201800311
Subject(s) - chemistry , malononitrile , methylene , nitrile , dimer , combinatorial chemistry , substrate (aquarium) , organic chemistry , stereochemistry , catalysis , oceanography , geology
The reaction of chloroximes that have a protected amino group and active methylene nitriles under basic conditions has been shown to give functionalized 5‐aminoisoxazoles in yields of 37–81 %. This method has a broad substrate scope, including nitriles that contain either an electron‐withdrawing (i.e., CO 2 Me, CN, or SO 2 Me) or a heteroaryl group at the α‐position. Moreover, a malononitrile dimer was employed in analogous transformations, which led to the formation of polyfunctional isoxazolo[5,4‐ b ]pyridines. The selective removal of the protecting groups contained in the product demonstrated the utility of these compounds as advanced building blocks in early drug discovery programs.