A new method for synthesizing agomelatine

Abstract

The invention relates to a novel method for synthesizing agomelatine, comprising the steps of: based on 7-methoxy-1-naphthalene ethyl acetate (formula 2) as an initial raw material, obtaining 7-methoxy-1-naphthalene ethanol (formula3) through reduction, obtaining 7-methoxy-1-naphthalene ethyl methane sulfonate (formula 4) through methylsulfonylation reaction, reacting 7-methoxy-1-naphthalene ethyl methane sulfonate (formula 4) with sodium azide to obtain 1-(2-azide ethyl)-7-methoxynaphthalene (formula 5) and finally directly acetylizing 1-(2-azide ethyl)-7-methoxynaphthalene (formula 5) to obtain the end product: agomelatine. The method has the advantages of easiness in raw material obtaining, short synthetic route, few reaction steps, mild reaction conditions and easiness in separation and purification of each intermediate and is suitable for industrial production.

Description

technical field

[0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and in particular relates to a preparation method of antidepressant agomelatine. Background technique

[0002] Agomelatine, the chemical name is N-[2-(7-methoxy-1-naphthyl)ethyl]acetamide, and its structural formula is:

[0003]

[0004] Developed by the French company Servier and first launched in Europe in 2009. It is not only the world's first melatonin receptor agonist, but also 5-HT 2C receptor antagonists. Agomelatine has a good antidepressant effect, its onset is fast, and it has a good curative effect on depression and its accompanying symptoms such as anxiety and insomnia. It has few adverse reactions and high safety. It provides a good foundation for clinical treatment of MDD. New approach, with high value pharmacological properties.

[0005] Andrieux et al first reported the preparation method of agomelatine in the patent EP0447285 in 1991, and the proc...

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