89-21-4Relevant articles and documents
Experimental and Computational Studies towards Chemoselective C?F over C?Cl Functionalisation: Reversible Oxidative Addition is the Key
Jacobs, Emily,Keaveney, Sinead T.
, p. 637 - 645 (2020/12/07)
Catalytic cross-coupling is a valuable tool for forming new carbon-carbon and carbon-heteroatom bonds, allowing access to a variety of structurally diverse compounds. However, for this methodology to reach its full potential, precise control over all competing cross-coupling sites in poly-functionalised building blocks is required. Carbon-fluorine bonds are one of the most stable bonds in organic chemistry, with oxidative addition at C?F being much more difficult than at other C-halide bonds. As such, the development of methods to chemoselectively functionalise the C?F position in poly-halogenated arenes would be very challenging if selectivity was to be induced at the oxidative addition step. However, metal-halide complexes exhibit different trends in reactivity to the parent haloarenes, with metal-fluoride complexes known to be very reactive towards transmetalation. In this current work we sought to exploit the divergent reactivity of Ni?Cl and Ni?F intermediates to develop a chemoselective C?F functionalisation protocol, where selectivity is controlled by the transmetalation step. Our experimental studies highlight that such an approach is feasible, with a number of nickel catalysts shown to facilitate Hiyama cross-coupling of 1-fluoronapthalene under base free conditions, while no cross-coupling with 1-chloronapthalene occurred. Computational and experimental studies revealed the importance of reversible C?Cl oxidative addition for the development of selective C?F functionalisation, with ligand effects on the potential for reversibility also presented.
3-(5-CHLORO-2-OXOBENZO[D]OXAZOL-3(2H)-YL)PROPANOIC ACID DERIVATIVES AS KMO INHIBITORS
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Page/Page column 41; 49, (2015/07/07)
A compound of formula (I) or a salt thereof are provided wherein R1, X and R3 are defined in the specification, useful in the treatment of disorders mediated by KMO such as acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
KINASE INHIBITORS AND METHODS OF USE
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Page/Page column 83-84, (2010/04/03)
The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as mTor, tyrosine kinases, and/or lipid kinases such as PI3 kinase. Also provided in the present invention are methods of using these compositions to modulate activities of one or more of these kinases, especially for therapeutic applications.
