756488-62-7Relevant articles and documents
N -Alkylation of organonitrogen compounds catalyzed by methylene-linked bis-NHC half-sandwich ruthenium complexes
Botubol-Ares, José Manuel,Collado, Isidro G.,Jiménez-Tenorio, Manuel,Moutaoukil, Zakaria,Serrano-Díez, Emmanuel
supporting information, p. 831 - 839 (2022/02/03)
An efficient ruthenium-catalyzed N-alkylation of amines, amides and sulfonamides has been developed employing novel pentamethylcyclopentadienylruthenium(ii) complexes bearing the methylene linked bis(NHC) ligand bis(3-methylimidazol-2-ylidene)methane. The
Development of the Late-Phase Manufacturing Process of ZPL389: Control of Process Impurities by Enhanced Process Knowledge
Santandrea, Ernesto,Waldraff, Christine,Gerber, Gilles,Moreau, Ma?l,Beney, Pascal
supporting information, p. 1190 - 1205 (2021/05/06)
The development of the late-phase manufacturing process of the drug candidate ZPL389 and the strategies for the control of impurities are outlined in detail. Selective salt formation at several stages was pivotal to controlling the process impurities. The extensive optimization of the N-methylation of a Boc-protected amine with dimethyl sulfate and of a nucleophilic aromatic substitution without the use of metal catalysts led to a robust, scalable process. The process was demonstrated on a >100 kg scale. Overall, improved drug substance quality, higher yield, and reduction of the process mass intensity were achieved.
Direct Amidation of Carboxylic Acids through an Active α-Acyl Enol Ester Intermediate
Xu, Xianjun,Feng, Huangdi,Huang, Liliang,Liu, Xiaohui
, p. 7962 - 7969 (2018/06/18)
The development of a highly efficient and simple protocol for the direct amidation of carboxylic acids is described employing ynoates as novel coupling reagents. The transformation proceeds in good to excellent yields via in situ α-acyl enol ester intermediates formation under mild reaction conditions. This useful method has been demonstrated for a range of substrates to provide a succinct access to structurally diverse amides, including key intermediates of glibenclamide, tiapride hydrochloride, and nateglinide, and can be conducted on a mole scale.