http://rdf.ncbi.nlm.nih.gov/pubchem/patent/TW-I404705-B

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filingDate 2009-08-19-04:00^^<http://www.w3.org/2001/XMLSchema#date>
grantDate 2013-08-11-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_2c4d4472fdab0bd2b36063aa8047b03e
http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_c55fe992e1957ee4ba89444cddb5fbab
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publicationDate 2013-08-11-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber TW-I404705-B
titleOfInvention Novel analytical method for the image isomer of (3,4-dimethoxy-bicyclo[4.2.0]oct-1,3,5-trien-7-yl) nitrile and its application to ivabradine (IVABRADINE) Synthetic application
abstract Process for optical resolution of (3,4-dimethoxy-bicyclo[4.2.0]octa-1 ,3,5-trien-7-yl)nitrile (I) comprises separating enriched racemic or enantiomeric mixture of (3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien -7-yl)nitrile into its two enantiomers comprising (S)-(3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl)nitrile and (R)-(3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl)nitrile, by chiral chromatography. Independent claims are included for: (1) (S)-(3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl)nitrile (Ia); (2) (R)-(3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl)nitrile (Ib); (3) the synthesis of C-((S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-t rien-7-yl)-methylamine (V) comprising subjecting (Ia) to a reduction reaction; and (4) the synthesis of ivabradine or its salt, and hydrate comprising subjecting (I) to the optic resolution process for obtaining (Ia), transforming (Ia) to (V), transforming (V) to ((S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-ylmethyl)-carbamic acid ethyl ester (VI), reducing (VI) to ((S)-3,4-dimethoxy-bicyclo[4. 2.0]octa-1,3,5-trien-7-ylmethyl)-methyl-amine (III), and transforming (III) to ivabradine or 3-{3-[{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1 ,3,5-trien-7-yl]methyl}(methyl)amino]propyl}-7,8-dimethoxy-1,3,4,5-te trahydro-2H-3-benzazepin-2-one, which is optionally converted into addition salts with acid comprising hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, trifluoroacetic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, tartaric, maleic, citric, ascorbic, oxalic, methane sulfonic, benzenesulfonic and camphoric or its hydrates. - ACTIVITY : Cardiant; Vasotropic; Antianginal; Antiarrhythmic. - MECHANISM OF ACTION : None given.
priorityDate 2008-08-29-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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