64169-39-7Relevant articles and documents
Copper-catalysed cyanoalkylative cycloetherification of alkenes to 1,3-dihydroisobenzofurans: development and application to the synthesis of citalopram
Ha, Tu M.,Wang, Qian,Zhu, Jieping
supporting information, p. 11100 - 11103 (2016/09/19)
A copper-catalysed cyanoalkylative cycloetherification of alkenes was developed. Heating a solution of substituted (2-vinylphenyl)methanol in MeCN/MeOH (v/v 7/3) in the presence of a catalytic amount of copper(ii) tetrafluoroborate hydrate [Cu(BF4)2·6H2O], bathophenanthroline, K3PO4, BnOH and (tBuO)2 afforded 1,3-dihydroisobenzofurans (phthalanes) via formation of one C(sp3)-C(sp3) and one C(sp3)-O bonds. A concise synthesis of citalopram, a marketed anti-depressant drug, was accomplished by applying this novel synthetic transformation.
Structure-activity relationships for a novel series of citalopram (1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5- carbonitrile) analogues at monoamine transporters
Zhang, Peng,Cyriac, George,Kopajtic, Theresa,Zhao, Yongfang,Javitch, Jonathan A.,Katz, Jonathan L.,Newman, Amy Hauck
experimental part, p. 6112 - 6121 (2010/11/16)
(±)-Citalopram (1, 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1, 3-dihydroisobenzofuran-5-carbonitrile), and its eutomer, escitalopram (S-(+)-1) are selective serotonin reuptake inhibitors (SSRIs) that are used clinically to treat anxiety and depression. To further explore structure-activity relationships at the serotonin transporter (SERT), a series of (±)-4- and 5-substituted citalopram analogues were designed, synthesized, and evaluated for binding at the SERT, dopamine transporter (DAT) and norepinephrine transporter (NET) in native rodent tissue. Many of these analogues showed high SERT binding affinities (Ki = 1-40 nM) and selectivities over both NET and DAT. Selected enantiomeric pairs of analogues were synthesized and both retained enantioselectivity as with S- and R-1, wherein S > R at the SERT. In addition, the enantiomeric pairs of 1 and 5 were tested for binding at the homologous bacterial leucine transporter (LeuT), wherein low affinities and the absence of enantioselectivity suggested distinctive binding sites for these compounds at SERT as compared to LeuT. These novel ligands will provide molecular tools to elucidate drug-protein interactions at the SERT and to relate those to behavioral actions in vivo.
IMPROVED PROCESS FOR THE MANUFACTURE OF CITALOPRAM HYDROBROMIDE
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Page/Page column 10, (2008/06/13)
The present invention describes an improved process for the preparation of extremely pure 1-(4'-Fluorophenyl)-1-(3-dimethylaminopropyl)-5-phthalanecarbonitrile and its bromide salt (citalopram hydrobromide), which is a well known antidepressant. Other aspect of the invention are isolation of crystalline (4-Bromo-2-hydroxymethyl)phenyl-(4-fluorophenyl)-3-(dimethylaminopropyl)methanol (Bromodiol) and conversion of desmethylcitalopram which is formed during the cyanide exchange reaction, to Citalopram by heating with a mixture of formaldhyde and formic acid in chloroform. The resulting citalopram is conventionally purified using extraction methodology.