cas 143612-79-7, 3-(4-Chlorbutyl)-1H-indol-5-carbonitril

Articles about 143612-79-7Total 26 be found

Article title
Article abstract
Author
Journal number and time
Download

Practical and Scalable Manufacturing Process for a Novel Dual-Acting Serotonergic Antidepressant Vilazodone
Vilazodone combines the effects of a selective serotonin reuptake inhibitor with the 5-HT1A receptor partial agonist activity. Here, we report the development of a viable and scalable process for manufacturing vilazodone that features a convergent synthetic approach, with low cost and high purity. The key indole synthesis was improved to first make up the hydrazone intermediate and then modify a pendant hydroxy group to realize a much increased overall yield. This process was successfully used to prepare >2 kg of vilazodone hydrochloride with a total yield of 56.2% and purity of 99.93%.
Jin, Hongshan,Wu, Chengjun,Zhou, Shuhao,Xin, Yunting,Sun, Tiemin,Guo, Chun
p. 1184 - 1189
(2021)
Read Online

Allosteric IGF-1R inhibitors
Targeting allosteric protein sites is a promising approach to interfere selectively with cellular signaling cascades. We have discovered a novel class of allosteric insulin-like growth factor-I receptor (IGF-1R) inhibitors. 3-Cyano-1H-indole-7-carboxylic acid {1-[4-(5-cyano-1H-indol-3-yl)butyl] piperidin-4-yl}amide (10) was found with nanomolar biochemical, micromolar, cellular IGF-1R activity and no relevant interference with cellular insulin receptor signaling up to 30 ?M. The allosteric binding site was characterized by X-ray crystallographic studies, and the structural information was used to explain the unique mode of action of this new class of inhibitors.
Heinrich, Timo,Graedler, Ulrich,Boettcher, Henning,Blaukat, Andree,Shutes, Adam
p. 199 - 203
(2010)
Read Online

Alternative approach to synthesis of 3-(4-Chloro butyl)- 1H -indole-5-carbonitrile: A key intermediate of vilazodone hydrochloride, an antidepressant drug
An alternative and efficient telescopic approach to the synthesis of 3-(4-chloro butyl)-1H-indole -5-carbonitrile (2), a key intermediate in the synthesis of vilazodone hydrochloride (1), is described.
Anitha,Reddy, B. Sudhakar,Sekhar,Reddy, K. Venugopal,Chandrasekhar
p. 3563 - 3571
(2014)
Read Online

Continuous Flow Process for Reductive Deoxygenation of ω-Chloroketone in the Synthesis of Vilazodone
A continuous flow process for the reductive deoxygenation of 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile to 3-(4-chlorobutyl)-1H-indole-5-carbonitrile was developed using a continuous stirred tank reactor (CSTR) setup. The opportunity for process optimization as well as scale-up feasibility was investigated at a laboratory scale. Advantages of a continuous process such as increased product yield, minimized impurity formation, enhanced safety, and increased overall purity of the isolated material thereby avoiding a purification step were demonstrated. Both sodium borohydride and a borane·THF complex were explored as reducing agents in conjunction with iron trichloride which produced high purity 3-(4-chlorobutyl)-1H-indole-5-carbonitrile not requiring further purification in higher yield than the standard batch process.
Karadeolian, Avedis,Patel, Dineshkumar,Bodhuri, Prabhudas,Weeratunga, Gamini,Gorin, Boris
p. 1022 - 1028
(2018)
Read Online

A NaH-promoted N-detosylation reaction of diverse p-toluenesulfonamides
A NaH-mediated detosylation reaction of various Ts-protected indoles, azaheterocycles, anilines and dibenzylamine was reported. The method features cheap reagent, convenient operations, mild reaction conditions and broad substrate scope. Moreover, this study revealed that the loading of NaH in tosylation reactions of nitrogen-containing compounds with NaH as a base in DMA or DMF should be controlled due to the possibility of adverse detosylation.
Sun, Wanwan,Chen, Xiaobei,Hu, Ying,Geng, Huihui,Jiang, Yuanrui,Zhou, Yuxin,Zhu, Wenjing,Hu, Min,Hu, Haohua,Wang, Xingyi,Wang, Xinli,Zhang, Shilei,Hu, Yanwei
supporting information

(2020/10/05)

Preparation method of vilazodone intermediate
The invention relates to a preparation method of a vilazodone intermediate, which comprises the following steps: carrying out F-C alkylation reaction on a compound 1 raw material and 1-bromo-4-chlorobutane under the action of anhydrous zinc chloride, and carrying out one-step reaction to obtain a compound I, namely, the vilazodone intermediate. Compared with the prior art, the method has the advantages of short reaction route, easiness in post-treatment, high yield, cheap and easily available reagents used in the F-C reaction, convenience in operation, simplicity in post-treatment, low cost, small environmental pollution and suitability for industrial production of the vilazodone intermediate I.
-
Paragraph 0039-0043; 0044-0047

(2020/05/11)

An investigation of the synthesis of vilazodone
A novel synthetic route toward vilazodone is described by using 4-cyanoaniline and 5-bromo-2-hydroxybenzaldehyde as starting materials, with an overall yield of 24% and 99% purity. First, the intermediate (3-(4-chlorobutyl)-1H-indole-5-carbonitrile) is synthesized via diazotization of 4-cyanoaniline, followed by Fischer indole cyclization with 6-chlorohexanal. Subsequently, another intermediate, 5-(piperazin-1-yl)benzofuran-2-carboxamide, is generated via aromatic nucleophilic substitution of 5-bromobenzofuran-2-carboxamide with piperazine. Finally, vilazodone is obtained via nucleophilic substitution of the above two key intermediates by treatment with Et3N/K2CO3. In comparison to the original process, this route avoids the use of expensive and toxic reagents and resolves issues such as safety, environmental concerns, and high costs.
Hu, Fan,Su, Weike
p. 243 - 247
(2020/01/08)

Production process 3-(4-chlorobutyl) indole -5- carbonitrile (by machine translation)
The invention discloses 3 - (4 -chlorobutyl) indo- 5 5-carbonitrile production process, which comprises the following steps, adding :chlorobutyl chloride in a clean reactor: stirring and cooling, with nitrogen in the same reactor at, temperature, and stirring the mixture in a reactor, for one time, to complete dissolution in a solvent, and stirring and cooling by 5 °C, steps: Stirring of 4 - Cooling The reactor, with nitrogen gas in the same reactor at a temperature of about 5-10 °C DEG . The production process of the invention is simple and reliable, production cost, of a reactor in the same reactor is stirred and uniformly: DEG C 5 - and the product purity, is, more suitable for industrialized, large-scale preparation, of the same reactor, and the production process, conditions, are more suitable for industrialized mass preparation of the product in, the same reactor, respectively . (by machine translation)
-
Paragraph 0022; 0025-0036; 0039-0050; 0052-0065

(2020/05/11)

Preparation method of)-5- 3-(4- n-butylisocyanopyridyl (by machine translation)
The preparation method is simple, 3 - (4 - the) - 5 - method is simple, the, preparation 1 - (2 - method, is simple), and the preparation method, is simple, the preparation; method 1 - is simple, and the preparation) method is simple, and the method is easy and 3 - (4 - simple) - 5 - to operate . (by machine translation)
-
Paragraph 0065; 0066

(2019/12/25)

Processes for the Preparation of 3-(4-Halobutyl)-5-Cyanoindole
The present invention provides continuous flow processes for the preparation of the compound of Formula (1), an intermediate in the preparation of Vilazodone.
-
Paragraph 0092-0100; 0073-0082; 0083-0091

(2019/11/11)

Synthetic method of Viazolone intermediate 3-(4-chlorobutyl)-5-cyanoindole
The invention relates to a synthetic method of Viazolone intermediate 3-(4-chlorobutyl)-5-cyanoindole. The method specifically comprises performing a reaction on 5-cyanoindole with 1-bromo-4-chloro-2-butene to obtain 3-(4-chlorobutyl-2-alken-1-yl)-5-cyanoindole, and further performing double bond reduction to obtain the 3-(4-chlorobutyl)-5-cyanoindole. The synthetic method provided by the invention has a simple synthetic route and production process, the yields and qualities of target products are high, the use of Lewis acids such as acyl chloride, aluminum chloride and the like is avoided, and thus the environment pollution is reduced.
-
Paragraph 0052; 0053; 0054; 0055; 0056; 0059-0064

(2018/01/12)

Preparation method of 5-cyano-3-(4-chlorobutyl)-benzpyrole
The invention belongs to the filed of chemical synthesis and discloses a preparation method of 5-cyano-3-(4-chlorobutyl)-benzpyrole. The method comprises the following steps: synthesizing 5-cyano-3-(4-chlorobutyl)-benzpyrole from 4-cyano phenyl diazoamino tetrafluoroborate as a raw material and a zinc reagent solution of 6-bromine chloride hexane under an acid condition. The 5-cyano-3-(4-chlorobutyl)-benzpyrole has the advantages of being high in yield, simple in process, green and environmental-friendly, and has very good industrialization prospect.
-
Paragraph 0013; 0037-0048

(2017/09/01)

Intermediate the vera assists the alkone 5-cyano -3 (4-chlorobutyl)-indole new synthetic process
The invention discloses a new synthetic process of a vilazodone intermediate 5-cyano-3(4-chlorobutyl)-indole. The synthetic process comprises the steps of enabling 5-amino-formyl-indole and 4-chlorobutyryl chloride undergo a 3-bit acylation reaction and a dehydration reaction of an amido bond in the presence of a catalyst to produce 5-bit cyan, then performing a decarbonylation reaction in the presence of a reducing agent to generate a product, and finally refining by the product by use of methanol to obtain high-purity high-content 5-cyano-3(4-chlorobutyl)-indole. The process is concise, simple to operate and applicable to large-scale industrial production.
-
(2017/02/09)

[...] and its salt synthesis method (by machine translation)
The invention relates to a synthesis method of vilazodone and a salt thereof, belonging to the technical field of drug synthesis. The synthesis method comprises the following steps of: with 5-fluorin-2-hydroxybenzaldehyde as a raw material, subjecting the 5-fluorin-2-hydroxybenzaldehyde and acetobromamide to reaction under the action of an acid binding agent to obtain a compound as shown in the formula (I); subjecting piperazine and the compound (I) as shown in the formula (I) to reaction at the temperature of 100-140 DEG C under the action of alkaline to obtain a compound as shown in the formula (II); and subjecting 3-(4-chlorobutyl)-5-cyanoindole and the compound as shown in the formula (II) to reflux reaction for 14-18h under the actions of a catalyst and alkaline, and then, adding the product into an aqueous alkaline solution until a solid is separated out to obtain a compound as shown in the formula (III), namely the vilazodone, wherein the compounds as shown in the formulas (I), (II) and (III) respectively have the structural formulas in the specification. The synthesis method is low in production cost, environment-friendly, high in conversion ratio, few in byproducts, high in product yield and purity, good in quality and suitable for large-scale industrial production.
-
Paragraph 0041; 0055

(2017/01/23)

[...] intermediate and its salt synthesis method
The invention relates to a synthesis method of a vilazodone intermediate 5-(4-[4-(5-cyano-3-indyl)-butyl]-1-piperazinyl)benzofuran-2-carboxylic acid ethyl ester and a salt thereof, belonging to the technical field of drug synthesis. The synthesis method comprises the following steps of: dissolving 3-(4-chlorobutyl)-5-cyanoindole and a catalyst into an inorganic water solution under the protection of nitrogen gas, carrying out heating reflux, stirring, then, adding 5-(piperazinyl-1-yl)benzofuran-2-carboxylic acid ethyl ester and alkaline, reacting at the temperature of 80-110 DEG C for 4-6h, slowly pouring an aqueous alkaline solution while stirring at room temperature until a solid is separated out, and then, carrying out after-treatment to obtain the 5-(4-[4-(5-cyano-3-indyl)-butyl]-1-piperazinyl)benzofuran-2-carboxylic acid ethyl ester. The synthesis method is low in production cost, environment-friendly, high in operation safety, high in product yield and purity, good in quality and suitable for large-scale industrial production.
-
Paragraph 0030; 0044; 0046

(2017/02/28)

Vilazodone intermediate preparation method
The present invention provides a vilazodone intermediate preparation method. According to the method, a caproaldehyde compound is adopted as a starting material, and reacts with a phenylhydrazine or aniline compound, and the obtained compound is subjected to ring closure under catalysis of an acid to obtain 3-(4-chlorobutyl)-5-cyano indole. According to the present invention, the application of the acylation reaction catalyzed through the Lewis acid in the literature is avoided, and the step of the methylene obtaining through carbonyl reduction with red aluminum in the literature is avoided and is not easily achieved in the workshop; and the compound is the key vilazodone synthesis intermediate, and the method has characteristics of easily available raw materials, mild reaction condition, simple operation, easy process control, low cost, and easy industrial production.
-
Paragraph 0033; 0034; 0035; 0036

(2016/11/14)

A 3 - alkyl indole preparation method
The invention discloses a preparation method of 3-alkylindole. The method is characterized in that a compound with the structural formula represented by formula 2 reacts with a complex hydride in an organic solvent in the presence of an Lewis acid to obtain a compound with the structural formula represented by formula 1; and the Lewis acid is selected from aluminum trichloride, iron trichloride, boron trifluoride or zinc dichloride.
-
Paragraph 0042; 0043; 0044; 0045; 0052; 0055; 0058-0068

(2017/05/19)

PROCESS FOR THE PREPARATION OF VILAZODONE HYDROCHLORIDE AND ITS AMORPHOUS FORM
The present invention relates to an improved process for the preparation of vilazodone Hydrochloride and a process for preparation of novel pure amorphous form of vilazodone hydrochloride.
-
(2015/03/31)

CRYSTALLINE FORMS OF VILAZODONE HYDROCHLORIDE AND VILAZODONE FREE BASE
Provided are crystalline and amorphous vilazodone hydrochloride. Further provided are amorphous solid dispersions of vilazodone hydrochloride with pharmaceutically acceptable carries. Also provided is a process for the preparation of form I of vilazodone free base.
-
(2015/05/13)

4-(2-(6-SUBSTITUTED-HEXYLIDENE) HYDRAZINYL)BENZONITRILE AND PREPARATION THEREOF
The present teachings provide a compound of Formula (I-B): wherein R1-R10 are as described herein; a pharmaceutically acceptable salt of the compound, a geometric isomer of the compound, or a pharmaceutically acceptable salt of the geometric isomer. Also described are methods of preparing the same, as well as methods for preparing vilazodone using the same.
-
Paragraph 0065

(2014/01/17)

PROCESS FOR PREPARATION OF VILAZODONE AND INTERMEDIATES THEREOF
Provided is a process for the preparation of vilazodone, its intermediate compounds and pharmaceutically acceptable salts thereof. Solvates of vilazodone and processes for their preparation are also provided. A process for the preparation of amorphous vilazodone hydrochloride is further provided.
-
(2014/06/24)

IMPROVED PROCESS FOR PREPARING BENZOFURAN-2-CARBOXAMIDE DERIVATIVES
Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of benzofuran-2-carboxamide derivatives and their intermediates, or a pharmaceutically acceptable salt thereof, in high yield and purity. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of vilazodone or a pharmaceutically acceptable salt thereof in high yield and purity. Provided also herein is an improved and commercially viable process for the preparation of 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile, in high yield and purity, using novel intermediate compound 3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile.
-
Page/Page column 41; 42

(2014/01/18)

PROCESSES FOR THE PREPARATION OF 3-ALKYL INDOLES
This invention provides processes for preparation of 3-alkyl indoles of Formula 1 : wherein A1, A2 and A3 are independently selected from the group consisting of: H, X, OR1, CN, CONR22 and C02R3; R1 is C1-C6 alkyl; R2 is H or C1-C6 alkyl; R3 is C1-C6 alkyl; LG is a leaving group; X is a halogen; and n is 1, 2 or 3.
-
Page/Page column 16

(2014/04/03)

CRYSTALLINE FORMS OF VILAZODONE HYDROCHLORIDE AND VILAZODONE FREE BASE
Provided are crystalline and amorphous vilazodone hydrochloride. Further provided are amorphous solid dispersions of vilazodone hydrochloride with pharmaceutically acceptable carries. Also provided is a process for the preparation of form I of vilazodone free base.
-
(2013/12/03)

Scale-up synthesis of antidepressant drug vilazodone
A scale-up synthesis of antidepressant drug vilazodone was accomplished in five steps. Friedel-Crafts acylation of 1-tosyl-1H-indole-5-carbonitrile with 4-chlorobutyryl chloride, selective deoxygenation in NaBH4/CF 3COOH system coupled with ethyl 5-(piperazin-1-yl)-benzofuran-2- carboxylate hydrochloride, one-step deprotection and esterolysis, and the final ammonolysis led to the target molecule vilazodone in 52.4% overall yield and 99.7% purity. This convenient and economical procedure is remarkably applicable for scale-up production.
Hu, Bin,Song, Qiao,Xu, Yungen
p. 1552 - 1557
(2013/02/25)

Synthesis and structure-activity relationship in a class of indolebutylpiperazines as dual 5-HT1A receptor agonists and serotonin reuptake inhibitors
Systematic structural modifications of indolealkylphenylpiperazines led to improved selectivity and affinity within this class of 5-HT1A receptor agonists. Introduction of electron-withdrawing groups in position 5 on the indole raises serotonin transporter affinity, and the cyano group proved to be the best substituent here. 5-Fluoro and 5-cyano substituted indoles show comparable results in in vitro and in vivo tests, and bioisosterism between these substituents was supported by calculation of the molecular electrostatic potentials and dipole moments. Compounds showing promising in vitro data were further examined in ex vivo (p-chloroamphetamine assay) and in vivo (ultrasonic vocalization) tests. Optimization of the arylpiperazine moiety indicated that the 5-benzofuranyl-2-carboxamide was best suited to increase 5-HT transporter and 5-HT1A receptor affinity and to suppress D2 receptor binding. 5-{4-[4-(5-Cyano-3-indolyl)butyl]-1-piperazinyl}benzofuran-2- carboxamide 29 (vilazodone, EMD 68843) was identified as a highly selective 5-HT1A receptor agonist [GTPγS, ED50 = 1.1 nM] with subnanomolar 5-HT1A affinity [IC50 = 0.2 nM] and as a subnanomolar 5-HT reuptake inhibitor [RUI = 0.5 nM] showing a great selectivity to other GPCRs (e.g., D2, IC50 = 666 nM).
Heinrich, Timo,B?ttcher, Henning,Gericke, Rolf,Bartoszyk, Gerd D.,Anzali, Soheila,Seyfried, Christoph A.,Greiner, Hartmut E.,Van Amsterdam, Christoph
p. 4684 - 4692
(2007/10/03)