- Method for preparing lorcaserin
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The invention discloses a method for preparing lorcaserin. Specifically, the method comprises the steps: taking p-chlorophenylacetonitrile as an initial raw material, preparing p-chlorophenylethylamine through reduction; carrying out a reaction with p-toluenesulfonyl chloride to form an amino occupying intermediate; enabling the intermediate to carry out a reaction with monochloroacetone under analkaline condition to form N-(2-(4-chlorphenyl)ethyl)-4-methyl-N-(2-propionyl)benzenesulfonamide, and then carrying out reduction, chlorination, p-toluenesulfonyl removal and intramolecular Friedel-Crafts alkylation to synthesize 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzoazepine, carrying out L-(+)-tartaric acid resolution and alkalization on azepine to remove tartaric acid, and acting with hydrogen chloride diethyl ether to salify to prepare lorcaserin. The method has the characteristics of simple synthesis method, good reaction selectivity, high product purity, environmental protectionand low preparation cost.
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Paragraph 0035-0036; 0041
(2020/08/22)
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- MODIFIED-RELEASE DOSAGE FORMS OF 5-HT2C AGONISTS USEFUL FOR WEIGHT MANAGEMENT
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The present invention relates to methods for weight management that utilize modified-release dosage forms comprising (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine salts and crystalline forms thereof. The present invention further relates to (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine salts, crystalline forms thereof and modified-release dosage forms comprising them.
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Paragraph 1181; 1188; 1194-1196
(2019/05/30)
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- Preparation method of lorcaserin intermediate
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The invention discloses a preparation method of a lorcaserin intermediate (I). According to the preparation method, p-chlorobenzyl cyanide is taken as the primary raw material, and the lorcaserin intermediate (I) is obtained after reduction reactions and condensation reactions. The primary raw materials (p-chlorobenzyl cyanide and 1-chloro-2-propanol) are cheap and easily available; raw materials, which can easily get polluted and are explosive, such as sulfoxide chloride, hydrobromic acid, borane, and the like are not used; the preparation method will not produce a large amount of wastewater and is beneficial for the environment protection; moreover, the requirements on the protection of workers are lowered, and safe production is guaranteed. The route design is novel, the raw materials are easily available, the operation is simple and feasible, and the preparation method is environment-friendly and can be applied to massive industrial production.
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- Preparation method for hemihydrate lorcaserin hydrochloride
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The invention discloses a preparation method for hemihydrate lorcaserin hydrochloride. The preparation method comprises the following steps: (1) making a compound shown as a formula III react with ammonia to obtain a compound shown as a formula II; (2) under the protection of nitrogen gas, dissolving the compound shown as the formula II in an organic solvent, adding a hydrogen chloride solution of which the solvent is the organic solvent to salify, and adding water and cyclohexane to form a hemihydrate in order to obtain the compound shown as a formula I, wherein the organic solvent is isopropanol or 1,4-dioxane. In the preparation method disclosed by the invention, ammonium hydroxide substitutes for potassium carbonate in the prior art, so that unqualified ignition residues of a finial product caused by potassium chloride generated after salt removal can be avoided; an isopropoxide hydrochloride solution substitutes for the conventional hydrogen chloride gas, so that other impurities can be prevented from being introduced in a preparation process under the improper control of dosage and rate of the gas.
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Paragraph 0057; 0058; 0059; 0060; 0061; 0062; 0063; 0064
(2017/08/28)
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- A preparing method of (R,S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, a lorcaserin intermediate
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A preparing method of (R,S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine that is a lorcaserin intermediate is disclosed. The method includes (1) dehydrating a compound 1 and a compound 2 under catalysis by boric acid to generate an amide 3, (2) reducing the intermediate 3 with a borane dimethylsulfide complex to obtain a compound 4, and (3) subjecting the compound 4 to direct ring closing with the existence of aluminum chloride to generate the lorcaserin intermediate that is the (R,S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine that is the compound 6. The method avoids use of 3,4,5-trimethoxyphenylboronic acid that is an expensive reagent, thus reducing the cost. The method avoids use of thionyl chloride so that the method is environmental friendly. A step of hydroxy chlorination is reduced so that the method is simple in process. The conversion ratio of raw materials and the total yield of reactions are increased. The yield of the compound 6 is increased from 60% in a patent to 82%. The method is suitable for industrial production. A reaction equation is shown in the description.
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Paragraph 0023; 0095; 0096; 0097; 0092
(2016/10/17)
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- Preparation method of lorcaserin hydrochloride
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The invention relates to the field of medicinal chemistry, and specifically discloses a preparation method of lorcaserin hydrochloride namely (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride. The preparation method is characterized in that 4-chlorophenethylamine as a raw material is successively subjected to acylation and amino protection, allyl substitution, Friedel-Crafts alkylation, resolution and salifying to obtain lorcaserin hydrochloride. The preparation method of lorcaserin hydrochloride has the advantages of high yield, low cost, simple operation and the like, and is an economic and industrializable synthesis method.
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Paragraph 0050; 0051
(2017/01/09)
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- 1 - (phenethyl-amino) propane-2-ol compound or its salt for the preparation of
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The invention relates to a preparation method of 1-(phenethylamino) propane-2-alcoholic compounds or salts thereof, shown in a formula II. The preparation method comprises the following step: reacting a compound shown in a formula I with epoxy propane to generate a compound shown in the formula II. According to the preparation method provided by the invention, cheap and accessible raw materials are adopted to prepare a target compound through a one-step reaction, so that the preparation method is low in cost, simple and convenient to operate, high in yield, environmental-friendly and suitable for industrial production. The invention also relates to a preparation method of lorcaserin or salts thereof. The lorcaserin is prepared from the high-purity 1-((4-chlorophenethyl) amino) propane-2-alcohol or the salts thereof, thereby being beneficial to improvement of the quality and stability of the product.
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Paragraph 0076; 0083-0084; 0094-097
(2016/11/24)
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- PROCESSES FOR THE PREPARATION OF LORCASERIN
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The present invention relates to stable crystalline Form A of lorcaserin hydrochloride of Formula (IA) and processes for its preparation. The invention also relates to processes for the preparation of lorcaserin and pharmaceutically acceptable salts, solvates and hydrates thereof.
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Paragraph 0093; 0094
(2016/10/20)
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- Lorcaserin hydrochloride hemihydrate preparation method
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The invention provides a lorcaserin hydrochloride hemihydrate preparation method. The method comprises the following steps: taking ethylamine as an initial raw material, performing an aminolysis ring-opening reaction with epoxypropane, chloridizing the material, performing friedel-Crafts alkylation cyclization on the material, splitting the material with tartaric acid, dissociating tartrate and forming hydrochloride to obtain the lorcaserin hydrochloride hemihydrate. The preparation method has the characteristics of less reaction steps, mild reaction condition, low cost of a comprehensive reagent, less three wastes, simple post-treatment and simple operation, so that the preparation method has the advantage of brand new, economy and environmental protection, high efficiency, and realization of industrial production.
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Paragraph 0031; 0032; 0059; 0060
(2016/11/17)
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- A kind of products and intermediates green card color forest hydrochloride method for the preparation of (by machine translation)
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The invention relates to the field of pharmaceutical chemistry, in particular relates to a diet green card color forest hydrochloride method for the preparation of intermediates thereof. The utility model is characterized in that the preparation method comprises: to the chlorobenzene ethylamine as raw materials, after sequentially acidylated protecting amino group, allyl substituted, deprotected, gram alkylate tougheness, split, a green card color forest of the hydrochloric acid salt. green card color forest hydrochloric acid of the present invention and wherein the intermediate preparation method is low in cost, simple in operation, after treatment is convenient, is an economical, can be industrial synthetic method. (by machine translation)
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- METHOD OF RACEMISATION OF UNDESIRED ENANTIOMERS
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The present invention provides a very simple, efficient and economic technology for racemisation of amines, alcohols or thioalcohols where the chiral carbon (benzylic position) is located at the β-position of the heteroatom (amino, hydroxyl or mercapto group) or even more distant therefrom. Special focus is oriented in efficient and simple racemisation of an undesired enantiomer of a chiral pharmaceutically active ingredient, preferably lorcaserin or a salt thereof, preferably the hydrochloride salt thereof. The approach according to the invention enables a use of cheaper and shorter racemic synthetic schemes not requiring expensive and toxic reagents and catalysts. Present methodology enables industrialy convenient process.
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Page/Page column 34-36
(2015/02/02)
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- ADMINISTRATION OF LORCASERIN TO INDVIDUALS WITH RENAL IMPAIRMENT
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The present disclosure relates to methods for weight management in an individual in need thereof by determining the level of renal sufficiency of the individual and prescribing or administering a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-ben-zazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to the individual, provided that the individual has a level of renal sufficiency selected from the group consisting of: no renal impairment, mild renal impairment, and moderate renal impairment. In addition, the disclosure relates to a method for selecting an individual for treatment with (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-ben-zazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof from a plurality of individuals in need of weight management by determining the level of renal sufficiency of the individual and selecting the individual for treatment with (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-ben-zazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof if the individual has a level of renal sufficiency selected from the group consisting of: no renal impairment, mild renal impairment, and moderate renal impairment.
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Paragraph 0764
(2015/11/24)
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- Novel Synthesis of Antiobesity Drug Lorcaserin Hydrochloride
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A novel synthesis of antiobesity drug lorcaserin hydrochloride was accomplished in six steps. N-protection of 2-(4-chlorophenyl)ethanamine with di-tert-butyl dicarbonate, N-alkylation with allyl bromide, deprotection, intramolecular Friedel-Crafts alkylation, chiral resolution with l-(+)-tartaric acid, and the final salification led to the target molecule lorcaserin hydrochloride in 23.1% overall yield with 99.9% purity and excellent enantioselectivity (>99.8% ee). This convenient and economical procedure is remarkably applicable for scale-up production.
- Zhu, Qihua,Wang, Junwei,Bian, Xueguo,Zhang, Lingzhi,Wei, Ping,Xu, Yungen
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p. 1263 - 1267
(2015/09/28)
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- FAST-DISSOLVE DOSAGE FORMS OF 5-HT2C AGONISTS
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Salts of the 5-HT2 c-receptor agonist (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, and dosage forms comprising them that are useful for, inter alia, weight management
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Page/Page column 87
(2012/03/26)
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- SALTS OF LORCASERIN WITH OPTICALLY ACTIVE ACIDS
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Salts of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine with optically active acids, and pharmaceutical compositions comprising them that are useful for, inter alia, weight management.
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Page/Page column 84-85
(2012/03/26)
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- Processes for the Preparation of 8-Chloro-1-Methyl-2,3,4,5-Tetrahydro-1H-3-Benzazepine and Intermediates Related Thereto
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The present invention provides processes, methods and intermediates for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, salts, hydrates and crystal forms thereof which are useful as serotonin (5-HT) receptor agonists for the treatment of, for example, central nervous system disorders such as obesity.
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Page/Page column 7; 12-13
(2009/06/27)
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- PROCESSES FOR PREPARING (R)-8-CHLORO-1-METHYL-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPINE AND INTERMEDIATES THEREOF
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The present invention provides processes and intermediates for the preparation of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and salts thereof which are useful as serotonin-2C (5-HT2C) receptor agonists for the treatment of, for example, obesity.
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Page/Page column 25-26
(2008/12/06)
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- BENZAZEPINE DERIVATIVES USEFUL FOR THE TREATMENT OF 5HT2C RECEPTOR ASSOCIATED DISEASES
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The present invention relates to certain 1-substituted-2,3,4,5-tetrahydro-3-benzazepine derivatives of Formula (I), that are modulators of the 5HT2C receptor. Accordingly, compounds of the present invention are useful for the prophylaxis or treatment of 5HT2C receptor associated diseases, conditions or disorders, such as, obesity and related disorders.
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