US 9,809,554 B2
Process for preparing ivabradine
Mara Sada, Segrate (IT); Faris Garis, Segrate (IT); and Giorgio Bertolini, Segrate (IT)
Assigned to OLON S.p.A., Rodano (Milan) (IT)
Appl. No. 14/892,771
Filed by OLON S.p.A., Rodano (Milan) (IT)
PCT Filed May 19, 2014, PCT No. PCT/IB2014/000762
§ 371(c)(1), (2) Date Nov. 20, 2015,
PCT Pub. No. WO2014/188248, PCT Pub. Date Nov. 27, 2014.
Claims priority of application No. MI2013A0830 (IT), filed on May 22, 2013.
Prior Publication US 2016/0107998 A1, Apr. 21, 2016
Int. Cl. C07D 223/16 (2006.01); B01J 23/44 (2006.01)
CPC C07D 223/16 (2013.01) [B01J 23/44 (2013.01)] 9 Claims
 
1. A process for preparing ivabradine hydrochloride of formula (I)

OG Complex Work Unit Drawing
comprising
a) reacting 3-(3-chloropropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one with (1S)-4,5-dimethoxy-1-[(methylamino)methyl] benzocyclobutane in suitable solvent;
b) reacting the 3-[3-[[[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl]methylamino]propyl]-1,3-dihydro-7,8-dimethoxy-2H-3-benzazepin-2-one obtained in step a) with HCl in a suitable solvent to obtain 3-[3-[[[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl]methylamino]propyl]-1,3-dihydro-7,8-dimethoxy-2H-3-benzazepin-2-one hydrochloride;
c) further obtaining 3-[3-[[[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl]methylamino]propyl]-1,3-dihydro-7,8-dimethoxy-2H-3-benzazepin-2-one hydrochloride obtained in step b) as a solid hydrochloride salt;
d) dissolving the solid hydrochloride salt from step c) in a C1-C4 alcohol solvent; and
e) hydrogenating the dissolved 3-[3-[[[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl]methylamino]propyl]-1,3-dihydro-7,8-dimethoxy-2H-3-benzazepin-2-one hydrochloride to obtain the compound of formula (I).