New procedure for the synthesis of Ivabradine, {{3 - 3 - (7S) - 3,4 - dimetoxibiciclo - 4.2.0 octa - 1,3,5 - triennium 2008-2010 IL - 7 - amino propyl methyl}} - 7.8 - Dimethoxy - 1,3,4,5 - tetrahydro - 2H - - 2 - 3 - benzacepin Ona and his addition salts with a pharmaceutically acceptable acid

摘要

Concerning a procedure for the synthesis of Ivabradine of formula (i) which consists in the preparation of a compound of benzazepin - 2 - ona formula (vii) by reacting The Compound 3 - (7.8 - Dimethoxy - 2 - oxo - 1,2,4,5 - tetrahydro - 3H - 3 - 3 - benzazepin propanenitrile (IL) - Formula with a compound of formula (viii), (IX) in the presence of a Salt of a transition metal or lanthanide chloride such as COPPER (i), trifluorometanosulfonato YTTRIUM (iii), Copper (i) IODIDE, trifluorometanosulfonato lanthanum (iii), ent Re, in a Solvent such as n, N - Dimethyl sulfoxide, dimethylformamide, n-methylpyrrolidone,Among other things, to give the compound N - {[(7S) - dimetoxibiciclo [3.4 - 4.2.0] octa - 1,3,5 - triennium 2008-2010 - 7 - il] methyl} - 3 - (7.8 - Dimethoxy - 2 - oxo - tetrahydro - 3h 1,2,4,5 benzazepin - 3 - 3 - (IL) - propanimidamina Formula X) that Transforms in the compound of formula (vii) by the action of an agent Donor as tetraborohidruro SODIUM HYDRIDE, borane Complex morpholine borane Complex -, - Tell Me Tilamina; where r is H or Methyl. The Compound 3 - [3 - ({[(7S) - dimetoxibiciclo [3.4 - 4.2.0] octa - 1,3,5 - triennium 2008-2010 - 7 - il] methyl} amino) propyl] - 7.8 - Dimethoxy - 1,3,4,5 - tetrahydro - 2H - 3 - (2 - benzazepin - ona formula XI) is the product of the reaction of a compound of formula (vii) where r is a hydrogen Atom with a donor HYDRIDE was methylated with N - [3 - (3 - [(7S) - 3,4 - dimetoxibiciclo [4. 2.0] octa - 1,3,5 - triennium 2008-2010 - 7 - il] methyl} (methyl) amino) propyl] - 7.8 - Dimethoxy - 1,3,4,5 - tetrahydro - 2H - 3 - benzazepin - 2 - One (9)