METHOD FOR ENZYMATIC SYNTHESIS OF (7S)-1-(3,4-DIMETHOXYBICYCLO [4.2.0]OCTA-1,3,5-TRIENE-7-YL)N-METHYL METHANAMINE AND APPLICATION THEREIN IVABRADINE SYNTHESIS

• Main Authors: MORIS VARAS, JAVIER, LEFOULON, FRANÇOIS, MOREAU, SANDRINE PEDRAGOSA, MORIS VARAS, FRANCISCO
• Format: Patent
• Language: English
• Published: 11.01.2016
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; BEER; BIOCHEMISTRY; CHEMISTRY; ENZYMOLOGY; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

A method for synthesis of compound of for¬mula (IX), which value R1 is provided in the claims and, which is executed with enantioselective enzymatic acylation of racemic amine of formula (IV) with R1O-(CO)-OR1 carbonate by application of lipase dissolved in organic or water solvent or in their mix, at 25-40 °C tempe¬ra¬ture. Reduction of received compound of formula (IX) is executed by application of restorative agent: LiAlH4 or Red-Al, to produce compound of formula (I) applicable at ivabradine synthesis. Table: 5