882880-12-8Relevant articles and documents
Industry-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole
Chen, Weiming,Suo, Jin,Liu, Yongjian,Xie, Yuanchao,Wu, Mingjun,Zhu, Fuqiang,Nian, Yifeng,Aisa, Haji A.,Shen, Jingshan
, p. 852 - 857 (2019/04/01)
Efforts toward route evaluation and process optimization for the preparation of brexpiprazole (1) are described. Starting from commercially available dihydroquinolinone 11, a three-step synthesis route composed of O-alkylation, oxidation, and N-alkylation was selected for industry-oriented process development aiming to reduce side reactions and achieve better impurity profiles. The reaction conditions of the three steps were investigated, and the control strategy for the process-related impurities was established. The optimized process was validated on the kilogram scale and now is viable for commercialization, with the results of not less than 99.90% purity of 1 (by HPLC) and not more than 0.05% of persistent impurities 15 and 16.
Synthesis of 1,4-bis[3,4-dihydro-2-(1H)-quinoline-7-oxo] butane
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Paragraph 0017, (2017/10/13)
The invention aims to provide a novel preparation method of an aripiprazole process impurity 1,4-bis[3,4-dihydro-2-(1H)-quinoline-7-oxo] butane, provides a basis for qualitatively and quantitatively analyzing impurities in a drug, has important meaning in synthesizing high quality aripiprazole, and provides a powerful guarantee for safe medication of a patient.
A PROCESS FOR PURIFICATION OF 7-(4-BROMOBUTOXY)-3,4 DIHYDROCARBOSTYRIL, AN INTERMEDIATE FOR MANUFACTURE OF ARIPIRAZOLE
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Page/Page column 8-9, (2010/11/30)
A process for the purification of 7- (4-bromobutoxy)-3,4- dihydrocarbostyril, substantially free of dimer impurity, said process comprising providing a solution of crude 7- (4-bromobutoxy)-3,4- dihydrocarbostyril containing the dimer impurity in an organic solvent selected from the group of halogenated hydrocarbon solvent, aromatic hydrocarbon, alcohols, alkyl esters of C1-C4 alkanoic acids, ethers, diethyl ester and ketones ; converting to a salt by the addition of an inorganic acid; separation of 1,4-bis [3,4-dihydro-2 (1H)-quinolinone-7-oxy] butane salt (dimer impurity salt) from the mixture, based on the difference in at least one physical property of 7- (4-bromobutoxy)-3,4- dihydrocarbostyril salt and the salt of dimer impurity; liberating the 7- (4-bromobutoxy)-3,4- dihydrocarbostyril salt by treating with an inorganic base; precipitating 7- (4-bromobutoxy)-3,4- dihydrocarbostyril by adding an anti-solvent.