882880-12-8

Usage

Uses

Used in Pharmaceutical Industry:
2(1H)-Quinolinone,7,7'-[1,4-butanediylbis(oxy)]bis[3,4-dihydrois used as an impurity in the process for the preparation of Aripiprazole (A771000), which is an antipsychotic medication used to treat schizophrenia, bipolar disorder, and depression.
Used in Pharmaceutical Industry:
2(1H)-Quinolinone,7,7'-[1,4-butanediylbis(oxy)]bis[3,4-dihydrois also used as an intermediate in the process for the preparation of Aripiprazole (A771000), playing a crucial role in the synthesis of this important medication.

Upstream product

• 6940-78-9 4-chlorobutyl bromide 
• 22246-18-0 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone 
• 110-52-1 1,4-dibromo-butane 
• 119532-26-2 1-(2,3-dichlorophenyl)-piperazine hydrochloride 
• 129722-34-5 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone 
• 952308-47-3 7-(4-iodobutoxy)-3,4-dihydroquinolin-2(1H)-one 
• 110-56-5 1,4-dichlorobutane 
• 120004-79-7 7-(4-chlorobutoxy)-3,4-dihydroquinoline-2(1H)-one 

Relevant academic research and scientific papers

Industry-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole

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

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.

Brexpiprazole impurity compound and preparation method thereof

The invention discloses a brexpiprazole impurity compound and a preparation method thereof. The impurity compound can be one or more of a compound I, a compound II, a compound III and a compound IV. The invention also discloses a use of the impurity compound in the control of the quality of brexpiprazole.

Efficient synthesis of deuterium labeled hydroxyzine and aripiprazole

Hydroxyzine and aripiprazole are active pharmaceutical ingredients that have been largely acknowledged for their antipsychotic properties. Deuterium labeled isotopes of hydroxyzine and aripiprazole are internal standards that can aid in the further research of non-isotopic forms via quantification analysis using HPLC-MS/MS. The synthesis of hydroxyzine-d8 was accomplished by coupling piperazine-d8 with 4-chlorobenzhydryl chloride followed by the reaction of the first intermediate with 2-(2-chloroethoxy) ethanol to afford 11.7% of hydroxyzine-d8 with 99.5% purity. The synthesis of aripiprazole-d8 was also achieved in two steps. 1,4-Dibromobutane-d8 reacted with 7-hydroxy-3,4-dihydro-2(1H)-quinolinone. The first intermediate was then coupled with 1-(2, 3-dichlorophenyl)piperazine hydrochloride to produce 33.4% of aripiprazole-d8 with 99.93% purity.

A PROCESS FOR PURIFICATION OF 7-(4-BROMOBUTOXY)-3,4 DIHYDROCARBOSTYRIL, AN INTERMEDIATE FOR MANUFACTURE OF ARIPIRAZOLE

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.

AN IMPROVED PROCESS FOR THE PREPARATION OF ARIPIPRAZOLE

The present invention relates to an improved process for the preparation of 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydro-2(1H)-quinolinone of Formula (I).

Process for the manufacture of aripiprazole by using purified carbostyril compounds such as 7-(4-halobutoxy)-3,4-dihydro-2(1H)-quinolinones

The present invention provides a process for purifying carbostyril derivatives such as 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone and 7-(4-chlorobutoxy)-3,4-dihydro-2(1H)-quinolinone and aripiprazole by passing a solution of the material in an organic solvent through a suitable absorbing material.

Synthesis and characterization of related compounds of aripiprazole, an antipsychotic drug substance

Three related compounds of aripiprazole were identified during the synthesis. These related compounds were synthesized and characterized by their respective spectral data. Copyright Taylor & Francis Group, LLC.

Process for the preparation of aripiprazole

The present invention relates to an improved process for the preparation of 7-[4[-(2,3-dichlorophenyl) -1-piperazinyl]butoxy]3,4-dihydro-2-(1H) quinolinone (Aripiprazole) having dimer impurity less than 0.15%, particularly, the present invention relates to an improved process for the preparation of 7-(4-chlorobutoxy)-3,4-dihydrocarbostyril of formula (I) having dimer impurity less than 0.5% comprising a step of, reacting 7-hydroxy-tetrahydroquinolinone of formula (III) with 1-bromo-4-chlorobutane in the presence of a base in a solvent.

Processes for preparing and purifying carbostyril compounds such as aripiprazole and 7-(4-halobutoxy)-3,4-dihydro-2(1H)-quinolinones

The present invention provides several improved processes for preparing aripiprazole, wherein the first step comprising reacting 7-HQ with a 1,4-disubstituted-butane in biphasic reaction mixture or in a single phase solvent to obtain a 7-(4-halobutoxy)-3,4-dihydro-(1H)-quinolinone (7-HBQ) and the second step comprising reacting the 7-HBQ and 1-(2,3-dichlorophenyl)piperazine or an acid addition salt thereof in a biphasic reaction medium containing water and a water-immiscible solvent to obtain aripiprazole. Also provided are methods of purifying the 7-HBQs and aripiprazole.