Title:
イバブラジンおよび薬学的に許容され得る酸とのその付加塩の新たな合成方法
Document Type and Number:
Japanese Patent JP5107382
Kind Code:
B2
Abstract:
Preparing tetrahydro-benzo[d]azepin-2-one compounds (A) comprises: reacting 3-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-propionitrile (VIII) with (3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-methyl-amine (IXa) in the presence of e.g. lanthanide in a solvent to obtain N-(3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-3-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N-methyl-propionamidine (Xa) in its racemic or optically active form; and transforming (Xa) by the action of a hydride donor. Preparing tetrahydro-benzo[d]azepin-2-one compounds (A) comprising 3-{3-[(3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-methyl-amino]-propyl}-7,8-dimethoxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one (ivabradine) (I) and 3-{3-[(3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-amino]-propyl}-7,8-dimethoxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one (II) in their racemic or optically active form comprises: reacting 3-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-propionitrile (VIII) with (3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-methyl-amine (IXa) or C-(3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-yl)-methylamine (IXb) in the presence of transition metal or lanthanide in a solvent to obtain N-(3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-3-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N-methyl-propionamidine (Xa) or N-(3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-3-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-propionamidine (Xb) in its racemic or optically active form; and transforming (Xa) or (Xb) by the action of a hydride donor. Independent claims are included for: (1) 3-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-propionitrile (VIII); (2) N-(3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-3-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N-methyl-propionamidine (Xa); and (3) N-(3,4-dimethoxy-bicyclo[4.2.0]octa-1(6),2,4-trien-7-ylmethyl)-3-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-propionamidine (Xb). ACTIVITY : Cardiant; Vasotropic; Antianginal; Antiarrhythmic. MECHANISM OF ACTION : None given.
Inventors:
Jean-Louis Perillon
Aime desanges
Bernard Selkis
Aime desanges
Bernard Selkis
Application Number:
JP2010076768A
Publication Date:
December 26, 2012
Filing Date:
March 30, 2010
Export Citation:
Assignee:
Réra Bora Toir Servier
International Classes:
C07D223/16; A61K31/55; A61P9/00; C07B53/00; C07B57/00; C07B61/00
Domestic Patent References:
| JP2005298480A | ||||
| JP2005330263A | ||||
| JP5213890A |
Attorney, Agent or Firm:
Hajime Tsukuni
Fusayuki Saito
Fusayuki Saito
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