| 摘要 |
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. |
