- Method for preparing lurasidone and salt thereof
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The invention relates to a method for preparing lurasidone and a salt thereof. The method comprises the following steps: reacting (R,R)-1,2-bis(methanesulfonyloxymethyl)cyclohexane and 3-(1-piperazinyl)-1,2-benzoisothiazole hydrochloride in acetonitrile in the presence of potassium carbonate to obtain an intermediate I; reacting the intermediate I with (3aR,4S,7R,7aS)-4,7-methylene-1H-isoindole-1,3(2H)-dione in DMF in the presence of potassium carbonate to prepare lurasidone free alkali; and reacting the lurasidone free alkali with hydrochloric acid in isopropanol to obtain lurasidone hydrochloride. The invention also relates to lurasidone and the salt thereof prepared by using the method, and application of lurasidone and the salt thereof in medicines for resisting psychosis, especially schizophrenia. The method disclosed by the invention has one or more advantages in a group consisting of simple process, high product yield, few impurities and the like.
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- Preparation method for lurasidone hydrochloride
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The invention discloses a preparation method for lurasidone hydrochloride. According to the preparation method, trans-1,2-cyclohexanedicarboxylic acid (SM-1) is used as a raw material and subjected to resolution, methyl esterification, reduction, methylsulfonylation, condensation, recrystallization and salt formation so as to eventually obtain lurasidone hydrochloride. The preparation method provided by the invention greatly reduces production cost and has the characteristics of high product yield, easy operation, low toxicity and suitability for industrial large-scale production.
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- Lurasidone key intermediate preparation method
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The present invention relates to a lurasidone key intermediate preparation method, and belongs to the technical field of compound synthesis. According to the method, when 4,-(1,2-benzisothiazol-3-yl)-(3aR,7aR)-octahydrospiro(2H-isoindole-2,1-piperazine)methanesulfonate is generated, 4-(1,2-benzisothiazol-3-yl)-1-piperazine is adopted as a raw material, the 4-(1,2-benzisothiazol-3-yl)-1-piperazine, (1R,2R)-1,2-bis(methanesulfonyloxymethyl)cyclohexane and potassium carbonate are subjected to a reaction in a solvent toluene, and a cyclodextrin phase transfer catalyst is added to the reaction system. According to the present invention, by using the cyclodextrin as the phase transfer catalyst, the incomplete reaction problem is solved, and the yield is substantially improved.
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Paragraph 0031; 0034
(2017/09/01)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF LURASIDONE BASE AND ITS SALT
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The present invention relates to an industrially feasible process for preparation of substantially pure Lurasidone base of formula Ia and its conversion to pharmaceutically acceptable salts such as hydrochloride salt and the like in significantly higher yield.
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Paragraph 15
(2017/09/27)
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- Method for preparing lurasidone with high purity and high yield
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The invention provides a method for preparing lurasidone with high purity and high yield. On the basis of an existing lurasidone preparation method, a small quantity of specific protic solvent is added in the preparation process of (R,R)-3a,7a-9H-isoindole-2-1'-[4'-(1,2-benzisothiazole-3-yl)] piperazine mesylate, so that the reaction rate is greatly increased, the time is shortened to 3 h from 23 h in the prior art, the yield is increased from 82% to 90%, the total yield is up to 71%, and the prepared finished product has the consistent quality with original drugs.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE
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Disclosed herein is an improved process for the preparation of Lurasidone and its pharmaceutically acceptable salts via novel intermediate and use thereof for the preparation of an antipsychotic agent useful for the treatment of schizophrenia and bipolar disorder. Further, present invention provides a cost effective and eco-friendly process for producing Lurasidone hydrochloride of formula (I) substantially free of residual solvent(s) at industrial scale.
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Page/Page column 21
(2016/05/24)
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- A method for preparing [...]
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The invention provides a method for preparing lurasidone. The preparation method comprises reacting 1-(1,2-benzisothiazol-3-yl) piperazine with (R, R)-1,2-bis(methylsulfonyl-methoxy) cyclohexane in a mixed solvent of acetonitrile/water in presence of bicarbonate as a base, adding toluene or xylene, separating an organic layer out, adding bicyclo [2.2.1] heptane-2,3-dicarboximide and carbonate into the organic layer and reacting to obtain lurasidone. The conventional separation and purification steps are omitted and the cost of production is greatly reduced; at the same time, the method has the characteristics of high yield and high purity of the product.
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Paragraph 0041; 0070; 0072
(2018/02/04)
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- PROCESS FOR THE INDUSTRIAL SYNTHESIS OF LURASIDONE
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Disclosed is a process for the industrial synthesis of Lurasidone from (1R,2R)-cyclohexane-1,2-diyldimethanol (1), 3-(piperazin-1- yl)benzo[d]isothiazole (3) and (3aR,4R,7R,7aS)-3a,4,7,7a-tetrahydro-4,7- methanoisobenzofuran-1,3-dione (6).). Said process is optimised to obtain Lurasidone with high yields and high purities by preparing highly pure synthesis intermediates, using critical raw materials and reagents in amounts close to the stoichiometric amounts, increasing productivity and reducing the costs and environmental impact of the process.
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Page/Page column 14
(2015/05/05)
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- SALTS AND HYDRATES OF ANTIPSYCHOTICS
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The present invention relates to a novel salt of (3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl)-piperazin-1-yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7-methanisoindol-1,3-dione and hydrates thereof, to methods for preparing the novel salt and its hydrates. In one aspect, the present invention provides a compound which is lurasidone dihydrochloride. In another aspect, the present invention provides a process for preparation of lurasidone dihydrochloride comprising: (i) mixing lurasidone free base in an organic solvent system; (ii) subjecting step (i) mixture to acid proton source; and (iii) isolating compound of lurasidone dihydrochloride.
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Paragraph 0051
(2015/07/02)
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- PROCESSES FOR MAKING ALKYLATED ARYLPIPERAZINE AND ALKYLATED ARYLPIPERIDINE COMPOUNDS INCLUDING NOVEL INTERMEDIATES
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Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively wherein, R1 and R2 are individually selected from hydrogen, alkyl, sub
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- PROCESS FOR PREPARING LURASIDONE AND INTERMEDIATE THEREOF
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A new method of synthesis of lurasidone, the substance of the chemical name (3aR,4S,7R,7aS)-2-(((1R,2R)-2-((4-(benzo [d]isothiazol-3-yl)piperazin-1 -yl)methyl)cyclohexyl)methyl)-hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione of structure 1 and its salts.
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- PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE
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Provided herein is a process for the preparation of the antipsychotic agent lurasidone hydrochloride useful for the treatment of schizophrenia.
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Page/Page column 22
(2014/03/26)
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- PROCESS FOR LURASIDONE
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The present invention provides a novel process for the purification of lurasidone substantially free of isomeric impurity.
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Page/Page column 5
(2014/07/21)
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- PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE
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Disclosed is a new and efficient process for the synthesis with high yields and purity of lurasidone hydrochloride, a medicament which is useful as a psychotropic substance. The process involves the preparation of lurasidone base in a reaction system not containing inorganic salts, followed by conversion of the latter to an addition salt with an organic carboxylic acid, which is finally converted to lurasidone hydrochloride.
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- PROCESS FOR PREPARING BENZISOTHIAZOL-3-YL-PEPERAZIN-L-YL-METHYL-CYCLO HEXYL-METHANISOINDOL-1,3-DIONE AND ITS INTERMEDIATES
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The present invention discloses process for preparing benzisothiazol-3-yl- piperazin-l-yl-methyl-cyclo hexyl-methanisoindol-l,3-dione and intermediates thereof.
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- NOVEL POLYMORPH OF LURASIDONE HYDROCHLORIDE
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The present invention provides a novel amorphous Form of lurasidone hydrochloride, process for its preparation and pharmaceutical compositions comprising it. In one aspect, the present invention provides an amorphous form of lurasidone hydrochloride. In another aspect, the present invention provides a process for the preparation of lurasidone hydrochloride amorphous Form, which comprises: a) dissolving lurasidone hydrochloride in a mixture of alcoholic solvent and water; and b) subjecting the resulting solution to lyophilization to obtain lurasidone hydrochloride amorphous form.
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- INTERMEDIATE COMPOUNDS AND PROCESS FOR THE PREPARATION OF LURASIDONE AND SALTS THEREOF
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The present invention relates to a process for the preparation of Lurasidone or a pharmaceutically acceptable salt thereof, a compound useful for the treatment of schizophrenia and bipolar disorder. The present invention further relates to processes for the preparation of Lurasidone intermediates, and to certain novel intermediates obtained by such processes.
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- PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE
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The instant invention discloses a process for the preparation of Lurasidone Hydrochloride preparation with lesser impurity profile comprises of isolating Lurasidone base as a solid whereby subjecting the base with isopropyl alcohol-hydrochloric acid.
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Page/Page column 19
(2014/01/09)
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- CRYSTALLINE LURASIDONE HYDROCHLORIDE
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The present invention provides crystalline lurasidone hydrochloride, processes for its preparation, a pharmaceutical composition comprising it and its use for the treatment of schizophrenia.
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Page/Page column 6
(2013/03/28)
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- PROCESS FOR THE PREPARATION OF AN ANTIPSYCHOTIC AGENT
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The present invention provides a process for the preparation of an antipsychotic agent useful for the treatment of schizophrenia.
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Page/Page column 15
(2012/10/18)
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- PROCESS FOR PRODUCING IMIDE COMPOUND
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The present invention provides an excellent industrial process for producing an imide compound hydrochloride. The process for producing an imide compound hydrochloride of the formula (2): or an enantiomer thereof, which comprises treating a compound of the formula (1): or an enatiomer thereof with an aqueous hydrochloric acid solution in a hydrophilic solvent, followed by crystallizing the resultant.
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Page/Page column 4-7
(2008/06/13)
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