- [...] intermediate and its salt synthesis method
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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.
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- SOLID STATE FORMS OF VILAZODONE AND VILAZODONE HYDROCHLORIDE
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The present invention provides solid state forms of Vilazodone and Vilazodone hydrochloride, processes for preparing these solid state forms, and pharmaceutical compositions comprising one or more of these solid state forms
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Paragraph 00285
(2013/06/06)
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- Scale-up synthesis of antidepressant drug vilazodone
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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
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p. 1552 - 1557
(2013/02/25)
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- Synthesis and structure-activity relationship in a class of indolebutylpiperazines as dual 5-HT1A receptor agonists and serotonin reuptake inhibitors
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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
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p. 4684 - 4692
(2007/10/03)
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- PIPERIDINES AND PIPERAZINES
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Piperidine and piperazine derivatives of the formula I STR1 wherein Ind is an indol-3-yl radical which is unsubstituted or mono-or polysubstituted by OH, OA, CN, Hal, COR 2 or CH 2 R 2, R 1 is benzofuran-5-yl or 2,3-dihydrobenzofuran-5-yl, chroman-6-yl, chroman-4-on-6-yl, 3-chromen-6-yl or chromen-4-on-6-yl, which is unsubstituted or monosubstituted by CN, CH 2 OH, CH 2 OA or COR 2,Q is C m H 2m,N or CR 3,A is alkyl having 1-6 C atoms,Hal is F, C1, Br or I,R 2 is OH, OA, NH 2, NHA or NA 2,R 3 is H, OH or OA and m is 2, 3 or 4,and their physiologically acceptable salts, are active on the central nervous system.
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