PROCESS FOR THE PREPARATION OF AGOMELATIN

• Main Authors: CHRISTOPHE HARDOUIN, JEAN-PIERRE LECOUVE, NICOLAS BRAGNIER
• Format: Patent
• Language: Croatian; English
• Published: 30.06.2012
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

Postupak za industrijsku sintezu spoja formule (I) naznačen time, da se izlaže reakciji spoj 7-metoksi-1-naftol formule (II): u kojem se kondenzira, u nazočnosti paladija, nakon konverzije hidroksi funkcije u odlazeću skupinu poput halogen, tosilatne ili trifluormetansulfonatne skupine, spoj formule (III): CH2=CH-R (III), u kojem R predstavlja skupinupri čemu R' i R", koji mogu biti jednaki ili različiti, svaki za sebe predstavljaju ravnu ili razgrananu skupinu Method for industrial synthesis of agomelatine comprises reaction of 7-methoxy-1-naphthol (II) with alkene compound (III) to obtain 7-methoxy-1-vinyl-naphthalene compound (IV); subjecting (IV) to catalytic hydrogenation to obtain methoxy-naphthalene compound (V); subjecting (V) to base or acid hydrolysis or with a binary reduction system/acid reduction system to obtain 2-(7-methoxy-naphthalen-1-yl)-ethyl amine (VI) or its hydrochloride; and reacting (VI) with sodium acetate and acetic anhydride to obtain agomelatine, which is isolated in the form of a solid. Method for industrial synthesis of agomelatine comprises reaction of 7-methoxy-1-naphthol (II), which is condensed in the presence of palladium after transformation of the hydroxyl group to the leaving group such as halogen, tosylate or trifluoromethanesulfonate group, with alkene compound of formula (CH 2=CH-R) (III), where the formed cycle is fused with a phenyl compound, to obtain a 7-methoxy-1-vinyl-naphthalene compound of formula (IV); subjecting (IV) to catalytic hydrogenation to obtain methoxy-naphthalene compound of formula (V); subjecting (V) to base or acid hydrolysis or with a binary reduction system/acid reduction system to obtain 2-(7-methoxy-naphthalen-1-yl)-ethyl amine (VI) or its hydrochloride; and reacting (VI) with sodium acetate and acetic anhydride to obtain agomelatine, which is isolated in the form of a solid. R : (-C(=O)-NH 2) or (-N(C(=O)-R 1>)(C(=O)-R 2>)); and either R 1>, R 2> : 1-6C linear or branched alkyl group; or R 1>, R 2> : 2-3C alkyl chain. An independent claim is included for the compound (IV) as an agent for synthesis of the agomelatine. [Image] ACTIVITY : Antidepressant; Hypnotic; Cardiovascular-Gen.; Gastrointestinal-Gen.; CNS-Gen.; Eating-Disorders-Gen.; Muscular-Gen.; Anorectic. MECHANISM OF ACTION : 5-Hydroxytryptamine 2C receptor antagonist.