- PROCESS FOR THE PREPARATION OF AGOMELATINE IN CRYSTALLINE FORM
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The present invention pertains to a process for the preparation of polymorph form X of agomelatine, which comprises providing agomelatine, and crystallizing agomelatine in the presence of at least one of an acid and a salt thereof, and to a polymorph form of agomelatine.
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Page/Page column 41
(2019/05/02)
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- 2 - (7 - Methoxy -1 - naphthyl) ethylamine preparation method
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The invention provides a preparation method of 2-(7-methoxy-1-naphthyl) ethylamine. The preparation method is characterized in that the raw material 4-toluene sulfonic acid1-(cyano methyl)-7-methoxynaphthalene-2-ester is reduced into the 2-(7-methoxy-1-naphthyl) ethylamine, a reducing agent used by the method is BH(OR)2, and R is propoxy or isopropoxy. The preparation method is few in reaction steps, high in yield, high in product purity and simple in post-processing.
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Paragraph 0015-0016
(2018/07/30)
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- Preparation method of Agomelatine
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The invention relates to a preparation method of Agomelatine. The preparation method comprises the steps of directly reducing a raw material 4-methylbenzenesulfonic acid 1-(cyano methyl)-7-methoxynaphthalene-2-estoral into 2-(7-methoxyl-1-naphthyl) ethylamine, and then further transforming into the Agomelatine. The preparation method of the Agomelatine provided by the invention is less in reaction step, high in yield/purity, and simple in aftertreatment.
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Paragraph 0022-0033
(2017/08/30)
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- PROCESS FOR THE PREPARATION OF AGOMELATINE
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The present invention relates to a method for economically and efficiently manufacturing agomelatine used as a medicine of depression, and a novel intermediate therefor. The manufacturing method comprises the steps of: (i) converting a hydroxy group of (7-methoxynaphthalene-1-yl)methanol of chemical formula II into a leaving group to obtain a compound of chemical formula III; (ii) coupling-reacting a compound of chemical formula IV or a compound of chemical formula V with the compound of chemical formula III, performing decarboxylation on the same, and obtaining 3-(7-methoxynaphthalene-1-yl)propanoic acid of chemical formula VI; (iii) performing Curtius rearrangement on the 3-(7-methoxynaphthalene-1-yl)propanoic acid of chemical formula VI, and obtaining 2-(7-methoxynaphthalene-1-yl)ethanamine of chemical formula VII; and (iv) performing an acetylization reaction on the 2-(7-methoxynaphthalene-1-yl)ethanamine of chemical formula VII.
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- A NOVEL PROCESS FOR THE PREPARATION OF TETRALIN AND NAPHTHALENE DERIVATIVES
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The present invention relates to a novel process for the preparation or tetralin and naphthalene derivatives, including Agomelatine and pharmaceutical acceptable salts thereof. Such compounds are considered to be interesting either as useful building blocks or due to their biological activity.
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- Simple and Efficient Process for the Large-Scale Preparation of Agomelatine: An Antidepressant Drug
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A simple and efficient process for the large-scale preparation of agomelatine (1), an antidepressant drug is, described. Agomelatine was prepared in a linear manner starting from readily available, inexpensive 2-naphthol. Key steps in the synthesis are Friedel-Crafts acylation of 2-naphthyl acetate with chloroacetyl chloride, reduction of keto intermediate, and nucleophilic displacement of chloro intermediate with sodium diformylamide. A systemic approach was described to streamline the process into a robust scalable process by controlling the impurities.
- Vujjini, Satish Kumar,Vyala, Sunitha,Badarla, Krishna Rao,Kandala, Sreenatha Charyulu,Bandichhor, Rakeshwar,Kagga, Mukkanti,Cherukupalli, Praveen
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p. 1864 - 1870
(2015/08/03)
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- A scalable synthesis of the antidepressant agomelatine by a tandem allylic chlorination-isomerization process
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A concise, scalable, and industrially applicable process for the synthesis of the antidepressant agomelatine is described. The process relies on a tandem allylic chlorination-isomerization sequence, on a tetralone-derived allyl carbinol, as the key transformation. The target compound is obtained in five steps from commercially available 7-methoxy-1-tetralone, in 52.3 % overall yield after final recrystallization. A tandem allylic rearrangement-isomerization sequence on a tetralone-derived allyl carbinol was applied for the preparation of agomelatine, a high-potential antidepressant agent with improved pharmacokinetic profile. The active pharmaceutical ingredient (API) was obtained in 52.3 % overall yield and excellent purity (> 99.5 %) by a simple process amenable to industrial-scale applications.
- Stathakis, Christos I.,Neokosmidis, Efstratios,Koftis, Theocharis V.
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supporting information
p. 6376 - 6379
(2016/02/18)
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- Synthesis and biological evaluation of novel naphthalene compounds as potential antidepressant agents
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In this study, a series of novel naphthalene compounds were synthesized and screened for their antidepressant-like activities in vitro and in vivo. Their values for two descriptors (ClogP, tPSA) of the blood-brain barrier (BBB) were calculated for early assessment of the central nervous system (CNS) drug-likeness. Seven of them (6d, 6i, 6k, 6o, 6p, 6s and 6t) demonstrated potential protective effects on corticosterone-induced lesion of PC12 cells although they cannot repair the irreversible oxidant injury to PC12 cells by hydrogen peroxide. Compounds with promising neurorestorative activities (6k, 6o and 6p) were further evaluated for their in vivo effects by forced swim test (FST) and open field test (OFT) in C57 mice models. The FST results showed that compounds 6k, 6o and 6p remarkably reduced the immobility time of the tested mice. Among them, compound 6k was the most potent one, much more effective than Agomelatine and comparable to Fluoxetine. The OFT results showed that mice treated with compound 6k traveled a longer distance than those treated with Agomelatine or Fluoxetine, indicating a better general locomotor activity. The paper also proposed a possible binding mode of compound 6k with glucocorticoid receptor by docking study. The in vitro cytotoxicity data on HEK293 and L02 cells suggested compound 6k to be a promising antidepressant candidate for subsequent investigation.
- Ang, Wei,Chen, Gong,Xiong, Li,Chang, Ying,Pi, Weiyi,Liu, Yuanyuan,Li, Chunlong,Zheng, Jiajia,Zhou, Liangxue,Yang, Bo,Deng, Yong,Yang, Shengyong,Luo, Youfu,Wei, Yuquan
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p. 263 - 273
(2014/06/24)
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- PROCESS FOR PREPARATION OF AGOMELATINE AND CRYSTALLINE FORM I THEREOF
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An improved process for the preparation of agomelatine of formula (I) and a new process for the preparation of crystalline form I of agomelatine are provided.
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- PROCESS FOR THE PREPARATION OF AGOMELATINE
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The present invention provides a process for the preparation of agomelatine and its intermediate compounds. The invention also provides an intermediate compound of agomelatine represented by Formula (V).
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Paragraph 0050; 0051; 0052
(2014/11/27)
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- AN IMPROVED PROCESS FOR PREPARATION OF AGOMELATINE
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The present invention provides an improved process for preparing agomelatine of formula (I). The process comprises reacting 7-methoxy tetralone with cyanoacetic acid in an organic solvent to obtain (7-methoxy-3,4-dihydro- 1 -naphthalenyl)acetonitrile of Formula (B); treating compound of Formula (B) with a catalyst to obtain (7-methoxy- 1 - naphthyl)acetonitrile of Formula (C); reducing compound of formula (C) with hydrogen in presence of Raney nickel in ammoniacal methanol medium and subsequently converting to a salt using hydrochloric acid to obtain 2-(7-methoxy- 1 -naphthyI)ethanamine hydrochloride of formula (D); iv) reacting compound of formula (D) with acetic anhydride or acetic chloride in an organic solvent in presence of a base and a catalyst to obtain agomelatine of Formula (I); and optionally purifying agomelatine of Formula (I). The present invention also provides a process for preparing polymorphic Form-I of agomelatine of formula (I) comprising treating agomelatine of formula (I) in a suitable organic solvent; and isolating polymorphic Form-I of agomelatine of formula (I).
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- PROCESS FOR THE PREPARATION OF AGOMELATINE
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The present invention provides a process for the preparation of agomelatine and its intermediate compounds. The invention also provides an intermediate compound of agomelatine represented by Formula (V).
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Page/Page column 10; 11
(2013/06/27)
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- Processes for the preparation of agomelatine and its intermediates
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Aspects of the present application relate to processes for the preparation of agomelatine and its intermediates which are used in manufacturing process of agomelatine.
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- PROCESS FOR THE PREPARATION OF AGOMELATINE
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The present invention relates to a process for the manufacture of N-[2-(7-methoxy-1-naphthalenyl) ethyl]acetamide (Agomelatine) with improved yield and reduced level of N- acetyl-N-[2-(7-methoxy-1-naphthalenyl) ethyl]acetamide impurity.
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Page/Page column 10
(2012/06/15)
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- PROCESSES FOR THE PREPARATION OF N-[2-(7-METHOXY-1-NAPHTHYL)ETHYL]ACETAMIDE
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The present invention relates to processes for the synthesis of N-[2-(7-methoxy-l - naphthethyl] acetamide, amorphous form of N-[2-(7-methoxy-l -naphthethyl] acetamide and pharmaceutical compositions thereof.
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- PROCESS FOR THE MANUFACTURE OF AGOMELATINE AND ITS INTERMEDIATE
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A process for the manufacture of agomelatine and its intermediate N-[2-(7-methoxy-1-naphthyl)ethyl] phthalimide comprises: reacting 7-methoxy-1-naphthyl ethanol (III) with benzenesulfonyl chloride to obtain 7-methoxy-1-naphthylethyl benzene sulfonate (IV), which is reacted with potassium phthalimide to produce N-[2-(7-methoxy-1-naphthyl)ethyl] phthalimide (II); and subjecting N-[2-(7-methoxy-1-naphthyl)ethyl] phthalimide (II) to alkaline hydrolysis and acetylation, to obtain agomelatine.
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- Process for the synthesis of agomelatine
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Process for the industrial synthesis of the compound of formula (I)
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Page/Page column 3
(2010/03/02)
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- Process for the synthesis and crystalline form of agomelatine
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A process for the industrial synthesis and a new crystalline form of the compound of formula (I): Medicinal products containing the same which are useful in treating disorders of the melatoninergic system.
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Page/Page column 6
(2008/06/13)
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