- Method and intermediate for synthesizing 7 - methoxy -1 - naphthalene acetonitrile
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The invention relates to the field of organic synthesis, and discloses a preparation method of 7 - methoxy -1 - naphthalene acetonitrile and an intermediate. The method comprises the following steps: (1) reacting 7 - methoxytetrahydro -1 -naphthyl ketone with cyanoacetic acid, (7 - methoxy -3, 4 -dihydro -1 - naphthyl) acetonitrile. (2) (7 - Methoxy -3, 4 - dihydro -1 - naphthyl) acetonitrile was subjected to a halogenation reaction to produce (7 - methoxy -3, 4 - dihydro -4 - halo -1 - naphthyl) acetonitrile. (3) (7 - Methoxy -3, 4 - dihydro -4 - halo -1 - naphthyl) acetonitrile dehalogenated hydrogen to give 7 - methoxy -1 - naphthalene acetonitrile. The method has the advantages of mild reaction conditions, less steps, simple operation and simple and easily available raw materials. There is no need to use harsh conditions, high cost catalysts or high risk chemicals. , As a new method for synthesizing 7 - methoxy -1 - naphthalene acetonitrile, the scheme provided by the invention has a good application prospect.
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- Preparation method of agomelatine intermediate
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The invention relates to a preparation method of an agomelatine intermediate. Specifically, the invention provides a preparation method of an agomelatine important intermediate 2-(7-methoxy-1-naphthyl)acetonitrile II, 7-methoxy-1-tetralone is used as an initial raw material, condensation and oxidation reactions are carried out to obtain the intermediate 2-(7-methoxy-1-naphthyl)acetonitrile, and the preparation method has the advantages of good yield, high product purity, simple reaction and easy operation, and is suitable for industrial production .
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Paragraph 0038-0062
(2021/03/31)
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- The preparation method of the agomelatine intermediate
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The invention relates to a preparation method of an agomelatine intermediate. The method specifically comprises the following steps: by using 7-methoxyl tetrahydronaphthalene-1-one and diethyoxyl phosphoryl ethyl acetate as initial raw materials, carrying out condensation, dehydrogenation, ammonolysis and dehydration to obtain the agomelatine intermediate, namely a compound shown in a formula (IV). The preparation method provided by the invention is economical in preparation process and suitable for massively preparing the agomelatine intermediate with high yield.
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Paragraph 0038; 0039; 0040
(2018/09/26)
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- A compound and its preparation method and application
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The invention provides a 1-cyan-1-(7-methoxyl-3, 4-dihdyro-1-naphthyl) methanol ester compound shown as a structural formula I described in the specification, wherein R is H, C1-C6 aliphatic groups or aryl. The invention further provides a preparation method of the compound and an application thereof in preparing agomelatine. The method of synthesizing agomelatine by the 1-cyan-1-(7-methoxyl-3, 4-dihdyro-1-naphthyl) methanol ester compound shown as the structural formula I is mild in condition, lower in production cost, higher in yield and fewer in impurities in end-products of reaction, and is more suitable for industrialized production.
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- 7-methoxy naphthyl acetonitrile synthesis method
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The invention discloses a 7-methoxy naphthylacetonitrile synthesis method, which comprises: 1) using 7-methoxy-3,4-dihydro naphthylacetonitrile as a raw material, adopting DDQ as a catalyst, carrying out an oxidation reaction on the 7-methoxy-3,4-dihydro naphthylacetonitrile and introduced oxygen in a halogenated alkane solvent to obtain 7-methoxy naphthylacetonitrile; and 2) extracting the reaction liquid obtained in the step 1), washing, concentrating, and re-crystallizing to obtain the 7-methoxy naphthylacetonitrile. According to the present invention, the 7-methoxy naphthylacetonitrile synthesis method has advantages of low cost, convenient post-treatment and less post-treatment sewage, wherein the by-product is water so as to provide the advantage of green environmental protection.
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Paragraph 0014; 0017-0023
(2017/04/28)
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- Method for synthesizing agomelatine important intermediate 7-methoxy naphthylacetonitrile
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The invention provides a method for synthesizing an agomelatine important intermediate 7-methoxy naphthylacetonitrile. According to the invention, 7-methoxy-3,4-naphthalene acetonitrile is taken as a raw material, 2,3-dicyano-5,6-dichlorobenzoquinone is taken as a catalyst, and the materials are subjected to an oxidation reaction with oxygen in a halogenated hydrocarbon solvent to obtain the intermediate 7-methoxy naphthylacetonitrile. The method is concise, the production cost is low, the integral yield of the reaction is high, product quality is good, environmental protection is realized, the method is convenient for industrial production, and has large popularization meaning.
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Paragraph 0020-0023
(2017/10/07)
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- Method for preparing important intermediate 7-methoxynaphthyl acetonitrile of Agomelatine
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The invention provides a method for preparing an important intermediate 7-methoxynaphthyl acetonitrile of Agomelatine. The method comprises the step of subjecting 7-methoxy-3,4-dihydronaphthyl acetonitrile, which serves as a raw material, to an oxidation reaction with oxygen gas in a haloalkane solvent in the presence of dichlorodicyan benzoquinone which serves as a catalyst, thereby obtaining the intermediate 7-methoxynaphthyl acetonitrile. The method is simple, the production cost is low, the overall yield of reaction is high, the product quality is good, and the method is environmentally friendly, so that the industrial production is facilitated, and the method has a great popularization significance.
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Paragraph 0017; 0019; 0020; 0021; 0022; 0023
(2017/09/29)
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- Method for synthesizing 7-methoxynaphthalene acetonitrile
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The invention provides a method for synthesizing 7-methoxynaphthalene acetonitrile. An intermediate 7-methoxynaphthalene acetonitrile is obtained by carrying out an oxidation reaction of 7-methoxy-3,4-naphthalene acetonitrile serving as a raw material, dichloro-dicyano-benzoquinone serving as a catalyst and oxygen in a halogenated hydrocarbon solvent. The method is simple, low in production cost, high in reaction overall yield, high in product quality, environmentally friendly and convenient in industrialized production, and has great popularization significance.
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Paragraph 0019; 0020; 0021; 0022
(2018/03/01)
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- Preparation method of agomelatine intermediate
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The invention discloses a preparation method of an agomelatine intermediate. The preparation method comprises steps as follows: firstly, 1-bromo-7-methoxynaphthalene is dissolved in an organic solvent, and a mixed solution is formed; elementary alkali metal and an initiator are added to a reaction bottle, the organic solvent is added to the reaction bottle and stirred uniformly, the prepared mixed solution is dropwise added slowly, when a reaction liquid is boiled slightly, the organic solvent is supplemented into the reaction bottle and stirring is started, the prepared mixed solution is dropwise added continuously, and a reaction liquid of a 1-bromo-7-methoxynaphthalene Grignard reagent is obtained after the heat preservation reaction; bromoacetonitrile is added to the organic solvent, a bromoacetonitrile mixed liquid is prepared, the prepared bromoacetonitrile mixed liquid is dropwise added slowly to the reaction liquid of the Grignard reagent, and (7-methoxy-1-naphthyl) acetonitrile is obtained after the heat preservation reaction and aftertreatment. With the adoption of the method, industrial production can be realized, 1-bromo-7-methoxynaphthalene is taken as a starting material, the cost can be saved, the product quality is stable, the yield is high, and the preparation method is applicable to large-scale industrial stable production.
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Paragraph 0012; 0014; 0015; 0016; 0017
(2017/12/09)
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- Preparation method of 2-(7-methoxyl-1-naphthyl) acetonitrile
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The invention discloses a preparation method of 2-(7-methoxyl-1-naphthyl) acetonitrile. 2-(7-methoxyl-1-naphthyl) acetonitrile is prepared through the two steps of a Wittig reaction and an aromatization reaction. The reaction route is short, the overall reaction yield is high, particularly, after a hydrogen acceptor is added in the step2, the obtained product yield is further increased, purity is also high, reaction conditions are mild, no reagent and solvent high in toxicity are involved, and the preparation method is suitable for industrialized production.
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Paragraph 0070-0079
(2016/11/17)
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- Method for preparing 2-(7-methoxy-1-naphthyl) acetonitrile
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The invention discloses a method for preparing 2-(7-methoxy-1-naphthyl) acetonitrile.2-(7-methoxy-1-naphthyl) acetonitrile is prepared sequentially through a Wittig reaction and a aromatization reaction, process conditions and reactants are optimized, the final product yield is increased, product quality is improved, reaction conditions are mild, the process is easy and convenient to operate, and reagents and solvents large in toxicity are not involved.
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Paragraph 0031; 0032
(2016/11/21)
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- Naphthalene derivatives and their application on the medicament
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The invention provides a number of naphthalene derivatives or stereoisomers, tautomers, nitrogen oxides, metabolites, pharmaceutically acceptable salts or prodrugs thereof which are used for excitement of melatonin receptors. The invention also discloses pharmaceutical compositions containing such compounds and application thereof in treatment of central nervous system dysfunction of mammals, especially human.
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Paragraph 0233; 0234; 0235; 0236
(2016/10/09)
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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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- A (7 - methoxy -1 - naphthyl) acetonitrile method for the preparation of
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The invention relates to a preparation method of (7-methoxy-1-naphthyl)acetonitrile, a compound represented by formula (I). (7-methoxy-3,4-naphthyl)acetonitrile, a compound represented by formula (II), is reacted with hydrogenation catalysts in the presence of 4A molecular sieves; and (7-methoxy-1-naphthyl)acetonitrile is obtained after separation. (7-methoxy-1-naphthyl)acetonitrile is an important intermediate for preparing agomelatine.
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Paragraph 0013-0014
(2017/04/03)
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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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Page/Page column 14
(2014/05/24)
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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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Page/Page column 17
(2014/01/17)
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- PROCESSES FOR THE PREPARATION OF AGOMELATINE USING NOVEL INTERMEDIATES
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Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of Agomelatine or a salt thereof, in high yield and purity, using novel intermediates.
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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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- AGOMELATINE AND PHARMACEUTICAL COMPOSITIONS THEREOF
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Agomelatine crystal, which is a drug for treating depression, and pharmaceutical compositions thereof are provided. The X-ray powder diffraction spectra of such agomelatine crystal, which is irradiated by Cu-Kα and showed by 20(degree), has characteristic diffraction peaks at 12.84, 13.84, 16.14, 18.56, 19.12, 20.86, 21.20, 23.84; its IR absorption pattern has characteristic absorption peaks at about 3234, 3060, 2940, 1638, 1511, 1436, 1249, 1215, 1184, 1032, 908, 828, 755, 588 cm-1; and its DSC endothermic transition temperature is 97.6°C. The use of the agomelatine crystal as an active ingredient in preparing a medicament for the treatment of depression is also provided.
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- PROCESSES FOR THE PREPARATION OF INTERMEDIATES OF N-[2-(7-METHOXY-1-NAPHTHYL) ETHYL] ACETAMIDE
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The present invention provides processes for the preparation of intermediates of N-[2-(7-methoxy-1-naphthyl) ethyl] acetamide. More particularly the present invention relates to processes for the preparation of the compound of structural formula II. Also provides Isolated solid (7-Methoxy-l-naphthyl)ethanamine compound of structural formula VI as freebase.
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Page/Page column 10
(2012/10/08)
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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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Page/Page column 41
(2012/07/27)
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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 2
(2010/03/02)
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- PROCESS FOR THE SYNTHESIS OF (METHOXY-1-NAPHTHYL) ACETONITRILE AND APPLICATION IN THE SYNTHESIS OF AGOMELATINE
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Process for the industrial synthesis of the compound of formula (I) Application of such process in the synthesis of agomelatine.
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Page/Page column 2
(2010/06/16)
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- SUBSTITUTED NAPHTHALENES
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Disclosed herein are substituted naphthalene-based melatonin (MT) receptor modulators and/or 5-HT receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 36
(2008/12/08)
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- Process for the synthesis of (7-methoxy-1-naphthyl)acetonitrile and its application in the synthesis of agomelatine
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A process for the industrial synthesis of the compound of formula (I) Application in the synthesis of agomelatine.
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Page/Page column 6
(2008/06/13)
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- Process for the synthesis of (7-methoxy--1-naphthyl) acetonitrile and its application in the synthesis of agomelatine
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A process for the industrial synthesis of the compound of formula (I) Application in the synthesis of agomelatine.
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Page/Page column 2
(2008/06/13)
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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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- Synthesis of naphthalenic melatonin receptor ligands
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A highly efficient and versatile synthetic approach to the synthesis of naphthalenic analogs of melatonin, compound 7, and its 2-alkyl substituted analog 8 is described. This approach features the novel synthesis of substituted 1-naphthyl acetonitrile 12 and 19 by nucleophilic addition of LiCH2CN to substituted 1-tetralone, followed by aromatization via a 2-step reaction sequence, dehydrogenation with DDQ and TsOH catalyzed dehydration.
- Chu,Li
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p. 621 - 629
(2007/10/03)
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