http://rdf.ncbi.nlm.nih.gov/pubchem/patent/HK-1141511-A1

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filingDate 2010-08-23-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_8558bc8bef16640260547da7ce437dbe
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publicationDate 2010-11-12-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber HK-1141511-A1
titleOfInvention Process for the resolution of enantiomers and application thereof in the synthesis of ivabradine
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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