- Chemoselective Hydrogenation of Nitroarenes Using an Air-Stable Base-Metal Catalyst
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The reduction of nitroarenes to anilines as well as azobenzenes to hydrazobenzenes using a single base-metal catalyst is reported. The hydrogenation reactions are performed with an air-and moisture-stable manganese catalyst and proceed under relatively mild reaction conditions. The transformation tolerates a broad range of functional groups, affording aniline derivatives and hydrazobenzenes in high yields. Mechanistic studies suggest that the reaction proceeds via a bifunctional activation involving metal-ligand cooperative catalysis.
- Zubar, Viktoriia,Dewanji, Abhishek,Rueping, Magnus
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supporting information
p. 2742 - 2747
(2021/05/05)
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- Preparation method of 1-[2-(2, 4-dimethylthiophenyl)-phenyl]piperazine
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The invention relates to a preparation method of 1-[2-(2,4-dimethylthiophenyl)-phenyl]piperazine. The method comprises the steps that 2,4-dimethylthiophenol and 1-halogen-2-nitrobenzene carry out a substitution reaction to prepare 2-(2,4-dimethylthiophenyl) nitrobenzene, 2-(2,4-dimethylthiophenyl) nitrobenzene is reduced to prepare 2-(2,4-dimethylthiophenyl)aniline, and 2-(2,4-dimethylthiophenyl)aniline and bis(2-chloroethyl)amine hydrochloride carry out a cyclization reaction to prepare 1-[2-(2,4-dimethylthiophenyl)-phenyl]piperazine. According to the preparation method, 2,4-dimethylthiophenol and 1-halogen-2-nitrobenzene are used as starting materials, and a substitution reaction, a reduction reaction and a cyclization reaction are carried out to prepare the target compound. The three-step reaction is low in cost, high in yield and easy to purify and industrialize.
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Paragraph 0021
(2020/07/12)
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- Metal-Free Cercosporin-Photocatalyzed C-S Coupling for the Selective Synthesis of Aryl Sulfides under Mild Conditions
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Aryl sulfides are important motifs of bioactive molecules, which are generally synthesized by transition metal-based coupling reactions under harsh conditions. Herein, we developed a new method that visible light along with cercosporin, produced by liquid fermentation and functioned as a cost-effective and environmentally friendly photocatalyst, prompted the selective synthesis of aryl sulfides through C–S coupling of thiols and diazonium salts under mild conditions. Furthermore, this method can also be performed with a great conversion by the direct use of cercosporin-containing fermentation supernatant as catalytic system without organic solvent extraction.
- Li, Jia,Bao, Wenhao,Zhang, Yan,Rao, Yijian
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supporting information
p. 7175 - 7178
(2019/11/16)
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- AN IMPROVED PROCESS FOR PREPARATION AND PURIFICATION OF VORTIOXETINE HYDROBROMIDE
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The present invention is related to an improved process for the preparation and purification of crystalline polymorph of Vortioxetine hydrobromide of Formula-I and Vortioxetine hydrochloride of Formula-Ia. The process according to present invention is operationally simple and suitable for industrial application which will avoid hazardous chemicals and eliminate column chromatography to get ICH quality of pharmaceutically acceptable active pharmaceutical ingredient having snow white appearance.
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Page/Page column 9
(2018/09/19)
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- Synthesis and biological evaluation of some bicyclic [2-(2,4-dimethylphenylthio)phenyl] aniline and its amide derivatives as potential antitubercular agents
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Abstract: In the present investigation, a series of bicyclic [2-(2,4-dimethylphenylthio)phenyl] aniline analogues were synthesized and characterized by IR, NMR (1H and 13C) and mass spectra. All newly synthesized 15 compounds were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H 37Ra in both active and dormant state using an established XTT Reduction Menadione assay (XRMA). The titled compounds exhibited minimum inhibitory concentration (MIC90) ranging from 0.05 to?>30 (μ g/mL). The potent four compounds were further evaluated in THP-1 infection model where they demonstrated significant antitubercular activity. All the ex vivo active were further evaluated for cytotoxic activity against THP-1, MCK-7 and HeLa cell lines in order to check selectivity index. All compounds were further screened against four different bacteria to assess their selectivity towards MTB. These derivatives could be considered as a precursor structure for further design of antituberculosis agent. Graphical Abstract: SYNOPSIS A series of bicyclic [2-(2,4-dimethylphenylthio)phenyl] aniline analogues were synthesized. All newly synthesized 15 compounds were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H 37Ra in both active and dormant state using an established XTT Reduction Menadione assay (XRMA).[Figure not available: see fulltext.].
- Patil, Yogesh,Shingare, Ramesh,Chakraborty, Shakti,Borkute, Rachana,Sarkar, Dhiman,Madje, Balaji
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- 1-[2-(2,4-dimethylphenylsulfydryl)phenyl]piperazine hydrochloride and preparation method thereof
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The invention discloses 1-[2-(2,4-dimethylphenylsulfydryl)phenyl]piperazine hydrochloride and a preparation method thereof. By means of the specific preparation method, the HPLC purity of vortioxetinehydrochloride is higher than 99.5%, and the content of
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Paragraph 0019; 0020
(2018/04/28)
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- fertile for the west sandbank synthetic method
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The invention discloses a synthetic method of vortioxetine. The synthetic method comprises the following steps of by adopting a compound as shown in a formula (I) as a raw material, carrying out substitution reaction on the compound and 2,4-dimethyl thiophenol (II) to generate 2-(2,4-dimethyl phenyl alkyl sulfide) nitrobenzene (III); reducing 2-(2,4-dimethyl phenyl alkyl sulfide) nitrobenzene (III) to obtain 2-(2,4-dimethyl phenyl alkyl sulfide) phenylamine (IV); cyclizing 2-(2,4-dimethyl phenyl alkyl sulfide) phenylamine (IV) and N,N-bis(2-chloroethyl)-4-methyl benzsulfamide (VI) to obtain Tos-protecting vortioxetine (V); and preparing vortioxetine (VII) from Tos-protecting vortioxetine (V) under the action of a phenol additive. The synthetic method disclosed by the invention has the advantages of easily available raw material, simple process, low cost and high purity, and is suitable for industrialized production.
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Paragraph 0040; 0041
(2017/08/25)
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- PROCESS FOR PREPARATION OF VORTIOXETINE HYDROBROMIDE
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The present invention provides a process for preparation of Vortioxetine hydrobromide (I). The present invention also relates to the novel intermediate and its use in preparation of vortioxetine hydrobromide (I).
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Page/Page column 40-41
(2017/03/14)
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- NOVEL POLYMORPHIC FORMS OF VORTIOXETINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention provides polymorphic forms of Vortioxetine of and its pharmaceutically acceptable salts. Specifically the present invention relates to the novel crystalline forms of Vortioxetine or its pharmaceutically acceptable salts. Moreover, the present invention also provides an amorphous form of Vortioxetine hydrobromide and a stable amorphous co-precipitate of Vortioxetine hydrobromide with pharmaceutically acceptable excipients.
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Paragraph 0180
(2017/08/01)
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- Preparation method of vortioxetine hydrobromide
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The invention relates to the technical field of preparation of vortioxetine hydrobromide, in particular to a preparation method of vortioxetine hydrobromide. The preparation method comprises the following steps: taking 2,4-dimethyl thiophenol as a raw material to react with o-bromonitrobenzene so as to generate a compound (IV); treating the compound (IV) via a normal pressure catalytic hydrogenation method to obtain a compound (V); treating the compound (V) via a Sandmeyer reaction to obtain a compound (VI); and reacting a compound (VII) with piperazine, and then performing a reaction with hydrobromic acid to generate a salt, thereby obtaining a target compound (I). The method for preparing vortioxetine hydrobromide is relatively short in route, relatively mild in reaction condition, simple, convenient and feasible in after treatment, and more suitable for industrial production requirements.
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Paragraph 0030
(2017/01/19)
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- METHOD OF PREPARING VORTIOXETINE
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The new method of preparing 1-(2-(2,4-dimethylphenylsulphanyl)pheny!)piperazine of formula (I) or its salt comprises a reaction of 2-(2,4-dimethylphenylsulphanyl)benzeneamine of formula (XI), wherein Me is methyl, with a suitable precursor of formation of piperazine ring of formula (Xll), wherein LG is a leaving group and R is hydrogen or a protective group, in a suitable organic solvent, wherein the reaction is carried out without presence of a base in a neutral or acidic environment. (Formulae (I), (XI), (XII))
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Page/Page column 6, 7
(2016/01/25)
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- PROCESS FOR THE PREPARATION OF AN ANTIDEPRESSANT AND THE INTERMEDIATES THEREOF
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The present invention relates to a process for the preparation of 1-[2-(2,4-dimethylphenylsulphanyl)phenyl]piperazine of formula (I), also known as vortioxetine, salts thereof, and intermediates useful for its synthesis.
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Paragraph 0064-0065
(2016/06/13)
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- A PROCESS FOR PREPARATION OF VORTIOXETINE AND POLYMORPHS THEREOF
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The present invention relates to an improved process for preparation of vortioxetine or pharmaceutically acceptable salts thereof. The present invention also relates to new process for the preparation of vortioxetine or pharmaceutically acceptable salts thereof. The present invention further relates to novel polymorphs of vortioxetine hydrobromide and process for preparation thereof.
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Page/Page column 30
(2016/06/15)
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- Preparation method of anti-depression drug 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (VI)
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The invention relates to a preparation method of an anti-depression drug 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (VI). The preparation method comprises the following steps: using 2,4-dimethyl thiophenol (I) as the initial raw material; condensing the 2,4-dimethyl thiophenol (I) with 2-halogenated nitrobenzene (II) to obtain 2-(2,4-dimethylphenylsulfanyl)nitrobenzene (III); reducing the 2-(2,4-dimethylphenylsulfanyl)nitrobenzene (III) to obtain 2-(2,4-dimethylphenylsulfanyl)aniline (IV); and performing loop closing on the 2-(2,4-dimethylphenylsulfanyl)aniline (IV) and bis-(2-chloroethyl)amine hydrochloride (V), so that the 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (VI) is prepared. The preparation method disclosed by the invention has the following advantages: the raw materials are low in costs and easy to obtain, the technology is simple, and the preparation method is economical and environmental-friendly as well as suitable for industrial production.
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Paragraph 0057; 0058
(2017/01/12)
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- PROCESSES FOR THE PREPARATION OF VORTIOXETINE HYDROBROMIDE
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The present invention relates to a process for the preparation of vortioxetine and its pharmaceutically acceptable salts.
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Page/Page column 29; 30
(2016/09/22)
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- Synthetic method for vortioxetine hydrobromide
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The invention provides a synthetic method for vortioxetine hydrobromide. Firstly, 2-nitro thiophenol and 2,4-dimethyl iodobenzene are reacted, an intermediate 2-(2,4-dimethyl phenyl sulfenyl) nitrobenzene, the intermediate is subjected to reduction, 2-(2,4-dimethyl phenyl sulfenyl) phenylamine is prepared, then 2-(2,4-dimethyl phenyl sulfenyl) phenylamine and bis(2-chloroethyl)amine hydrochloride are subjected to a cyclization reaction, vortioxetine is prepared, finally, vortioxetine is reacted with hydrobromic acid and is salified, and vortioxetine hydrobromide is prepared. The total yield of vortioxetine hydrobromide can reach 65%, the method has advantages of cheap and easily available initial raw materials and simple synthetic technology, and meets requirements of large-scale industrial production.
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Paragraph 0022
(2016/10/07)
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- PROCESS FOR THE PREPARATION OF VORTIOXETINE SALTS
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The invention relates to an improved process for the preparation of pharmaceutical active ingredients and also to high purity salts and pharmaceutical compositions prepared by said process. More particularly the invention relates to an economical process for the preparation of the compound having the international non-proprietary name (INN) vortioxetine and the chemical nomenclature l-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine. Vortioxetine corresponds to the following Formula Still more particularly the invention relates to the preparation of high purity vortioxetine L- (+)-mandelate salt of the Formula IX, the conversion of this salt into other highly pure salts and also to the formulation of said salts.
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Page/Page column 33
(2015/09/23)
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- SYNTHESIS OF VORTIOXETINE VIA (2,4-DIMETHYLPHENYL)(2-IODOPHENYL)SULFANE INTERMEDIATE
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The present invention provides a new synthetic process for the production of 1 -(2-((2,4-dimethylphenyl)thio)phenyl)piperazine (vortioxetine), a drug for the treatment of depression and anxiety, which is conducted via (2,4-dimethylphenyl)(2-iodophenyl)sulfane intermediate.
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Page/Page column 13; 14
(2015/11/03)
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- NEW PROCESS FOR THE SYNTHESIS OF 1-(2-((2,4-DIMETHYLPHENYL)THIO)PHENYL)PIPERAZINE
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The present invention provides new intermediate compounds or formulae (III) and (IVa), and salts thereof, and their use in a new synthetic process for the production of 1-(2-((2,4- dimethylphenyl)thio)phenyl)piperazine (vortioxetine) an experimental drug under development for the treatment of depression and anxiety.
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Page/Page column 15
(2014/10/18)
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- Electrochemical Reduction of Some o-Bis(phenylsulphonyl)benzene Derivatives. Effect of the Substrate Structure and of the Addition of Bases on the Product Distribution.
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A study of the electrochemical behaviour of the o-bis(phenylsulphonyl)benzene derivatives (1a-e) in dimethyl sulphoxide containing 0.1M-tetrabutylammonium tetrafluoroborate has been undertaken.The results from cyclic voltammetry, controlled-potential electrolysis, and coulometry strongly argue in support of a mechanism involving initial formation of the radical anion (1)-. which fragments into the ? radical (2) and PhSO2-.Competing pathways for (2) are (a) intramolecular homolytic arylation eventually leading to dibenzothiophene (4) together with dihydrodibenzothiophene (5) derivatives and (b) hydrogen-atom transfer leading to monosulphones (6).The fact that compounds (1a,b) undergo mainly cyclization, whereas the hydrogen-atom transfer predominates in the case of compounds (1c,d), indicates that the structure of the starting substrate is a major governing factor for the above competition.An explanation, based on a concomitance of steric effects of the methyl groups ortho to the phenylsulphonyl substituents, is given.Experiments carried out in the presence of different bases show that the intramolecular arylation leading to the cyclized product can occur also through an unprecedented chain mechanism whose efficiency, which increases as the strength and the concentration of the base is increased, is found in turn to be dependent on the substrate structure.Finally, when arenethiolates are used as bases, a third pathways (the nucleophile-radical coupling step of the SRN1 process) is found to compete for the intermediate ? radical (2) eventually leading to sulphides resulting from the overall substitution of an arylthio for a moiety in (1).When the intramolecular cyclization does not compete efficiently almost quantitative yields of sulphides are obtained via an SRN1 route.
- Novi, Marino,Garbarino, Giacomo,Petrillo, Giovanni,Dell'Erba, Carlo
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p. 623 - 632
(2007/10/02)
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