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US 2014/0024088 A1Published application
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
AssigneeLes Laboratoires Servier
InventorsSandrine PEDRAGOSA-MOREAU, François LEFOULON, Francisco MORIS VARAS, Javier GONZALEZ SABIN
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Abstract
Process for the enzymatic synthesis of the compound of formula (I), (7S)-1-(3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl)N-methyl methanamine: and application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid.
Claims12
A process for the synthesis of a compound of formula (IX):
- wherein R1 represents a linear or branched C1-C6alkyl, allyl or benzyl group, by enantioselective enzymatic acylation of a racemic amine of formula (IV):
- using a lipase (EC 3.1.1.3 in the international classification of enzymes),
- with a carbonate of formula R1O—(CO)—OR1, wherein R1 is as defined hereinbefore,
- in an amount ranging from 1 to 15 molar equivalents relative to the amine of formula (IV),
- in an organic or aqueous solvent, a mixture of organic solvents or a mixture of organic and aqueous solvents,
- at a concentration from 5 to 500 g/L of compound of formula (IV) per litre of solvent or mixture of solvents,
- at an E/S ratio of from 10/1 to 1/100, at a temperature from 25° C. to 40° C.
4 more elements
Dependencies are inferred from the claim text.