Process for the enzymatic synthesis of (7s)-1-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl) n-methyl methanamine, and application in the synthesis of ivabradine and salts thereof
The disclosure relates to a process for the enzymatic synthesis of the compound of formula (I), (7S)-1-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-y1) N-methyl methanamine by enzymatic acylation of the racemic amine of formula (IV) to yield the carbamate of formula (IX), which is then reduced using a reducing agent selected from LiAlH4 and Red-Al to yield the compound of formula (I)； the compound of formula (I) subsequently is either coupled with a compound of formula (X) or, in the presence of a reducing agent, subjected to a reductive amination reaction with a compound of formula (XI) to yield 3-{ 34 { [(7S)-3,4-dimethoxybicyclo [4.2.0]octa-1,3,5-trien-7-yl] methyl} (methypamino]-propyl} -7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one (commonly known as ivabradine, which is represented by formula (II)), which is then converted into an addition salt with a pharmaceutically acceptable acid, in anhydrous or hydrate form, wherein the compounds of formulae (IV), (IX), (X) and (XI) are as shown in the specification.
