A new method for synthesizing agomelatine

A technology of agomelatine and compounds, applied in the field of pharmaceutical chemical synthesis, can solve the problems of unfavorable large-scale production and high requirements for production equipment, and achieve the effects of simple operation, high industrial application value, and mild reaction conditions

Active Publication Date: 2015-09-30
CHINA PHARM UNIV
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

For example, CN200510071623.9 utilizes high-pressure hydrogenation to reduce (7-methoxy-1-naphthyl)acetonitrile (formula 10) to (7-methoxy-1-naphthyl)ethylamine under the effect of Raney nickel catalyst (Formula 11), this process needs to use a large amount of hydrogen, has higher requirements on production equipment, has certain dangers, and is not conducive to industrialized large-scale production

Method used

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  • A new method for synthesizing agomelatine
  • A new method for synthesizing agomelatine
  • A new method for synthesizing agomelatine

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Embodiment 1

[0027] Embodiment 1 prepares agomelatine

[0028] The preparation method of the present embodiment comprises the following steps:

[0029] The preparation of step 1 7-methoxy-1-naphthyl alcohol

[0030] 4.9 g of ethyl 7-methoxy-1-naphthalene acetate, NaBH 4 1.6g, ZnCl 2 2.7g of THF50ml solution was refluxed for 3 hours, TLC showed that the reaction was complete, cooled to room temperature, carefully added 100ml of dilute hydrochloric acid to quench the reaction; extracted with 200ml of ethyl acetate, combined organic layers, washed with saturated sodium chloride, dried over anhydrous sodium sulfate ; The solvent was distilled off under reduced pressure to obtain 3.8 g of an off-white solid with a melting point of 83-85° C. and a yield of 95%.

[0031] Preparation of step 2 7-methoxy-1-naphthyl ethyl methanesulfonate

[0032] 1.0 ml of methanesulfonyl chloride was added dropwise to a solution of 1.6 g of 7-methoxy-1-naphthyl ethanol and 1.5 ml of triethylamine in 25 ml of...

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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...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C233/18C07C231/10
Inventor 孙丽萍汪有亮李玉艳
Owner CHINA PHARM UNIV
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