Title:
（３，４−ジメトキシ−ビシクロ［４．２．０］オクタ−１，３，５−トリエン−７−イル）ニトリルの鏡像異性体を分割する新規な方法、およびイバブラジン合成における適用
Document Type and Number:
Japanese Patent JP5663154
Kind Code:
B2
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-trien-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-tetrahydro-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.
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Inventors:
ジャン−ミッシェル・ルレスティフ
ジャン−ピエール・ルクヴ
ダニエル・ドロン
エリック・ゴジョン
マリース・ファン
ジャン−ピエール・ルクヴ
ダニエル・ドロン
エリック・ゴジョン
マリース・ファン
Application Number:
JP2009197747A
Publication Date:
February 04, 2015
Filing Date:
August 28, 2009
Export Citation:
Assignee:
レ ラボラトワール セルヴィエ
International Classes:
C07C213/02; C07B57/00; C07B61/00; C07C217/48; C07C253/34; C07C255/47; C07D225/06
Attorney, Agent or Firm:
Patent business corporation Tsukuni
Hajime Tsukuni
Ito 佐保子
Keiko Ozawa
Toshio Miyake
Yasuhiro Kokuni
Yoko Tanaka
Yoshinori Ubukawa
Akio Shibata
Saito a fringe -- happy
Hajime Tsukuni
Ito 佐保子
Keiko Ozawa
Toshio Miyake
Yasuhiro Kokuni
Yoko Tanaka
Yoshinori Ubukawa
Akio Shibata
Saito a fringe -- happy