New process for the synthesis of Ivabradine and ADI - tion of the salts with a pharmaceutically acceptable acid

摘要

Synthesis process of ivabradine of formula (I) EMI FILE = "05013707_4" ID = "4" IMF = JPEG HE = 50 WI = 50 O 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-benzazepine-one, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof, characterized in the compound of the formula (V) EMI FILE = "05013707_2" ID = "2" IMF = JPEG HE = 50 WI = 50 where R1 and R2, which may be the same or different, each represents a linear or branched group (C1-C8) alkaloxy or together with the carbon atom that carry them, form a 1,3-dioxane,1,3-dinitrogen or 1.3-dinitrogen cyclic compounds must undergo hydrogenation catalysis, and then formula compound (VI) is obtained: EMI file = "05013707" U3 "id =" 3 "IMF = JPEG he = 50 wi = 50 wherein R1 and R2 are defined as above.it is subjected to a reaction with the compound of formula (VII) EMI FILE = "05013707_4" ID = "4" IMF = JPEG HE = 50 WI = 50 where HX represents a pharmaceutically acceptable acid, in the presence of hydrogen and a catalyst, to obtain directly, after completely filtering the catalyst and isolation, the additional salts of ivabradine with the HX acid, which is optionally subjected, when it is desired to obtain ivabradine free from the action of a base.