367514-88-3

Basic information

• Product Name: Lurasidone hydrochloride
• Synonyms: Lurasidonhydrochloride;Lurasidonhydrochlorid;(3aR,4S,7R,7aS)-2-[[(1R,2R)-2-[[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl]methyl]cyclohexyl]methyl]hexahydro-4,7-methano-1H-isoindole-1,3(2H)-dione hydrochloride;(1R,2S,3R,4S)-N-[(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinylMethyl]-1-cyclohexylMethyl]-2,3-bicyclo[2.2.1]heptanedicarboxyiMide hydrochloride;Latuda, SM 13496;Lurasidone Hydrochlorid;(3aR,4S,7R,7aS)-2-[(1R,2R)-2-[4-(1,2-Benzisothiazol-3-yl)piperazin-1-ylMethyl]cyclohexylMethyl]hexahydro-1H-4,7-Methanoisoindole-1,3-dione hydrochloride;4,7-Methano-1H-isoindole-1,3(2H)-dione, 2-[[(1R,2R)-2-[[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]methyl]cyclohexyl]methyl]hexahydro-, hydrochloride (1:1), (3aR,4S,7R,7aS)-
• CAS NO: 367514-88-3
• Molecular Formula: C₂₈H₃₆N₄O₂S*ClH
• Molecular Weight: 492.684
• EINECS: 200-659-6
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 367514-88-3.mol

Chemical Properties

• Melting Point: 198-205°C
• Flash Point: 9℃
• Appearance: /
• Storage Temp.: Refrigerator
• CAS DataBase Reference: Lurasidone hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Lurasidone hydrochloride(367514-88-3)
• EPA Substance Registry System: Lurasidone hydrochloride(367514-88-3)

Safety Data

• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25
• Safety Statements: 7-16-36/37-45
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 1
• Hazardous Substances Data: 367514-88-3(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Different sources of media describe the Uses of 367514-88-3 differently. You can refer to the following data:
1. Lurasidone is an atypical antipsychotic, inhibits Dopamine D2, 5-HT2A, 5-HT7, 5-HT1A and noradrenaline α2C with IC50 of 1.68 nM, 2.03 nM, 0.495 nM, 6.75 nM and 10.8 nM, respectively
2. An antipsychotic used for treatment of schizophrenia.

Definition

ChEBI: A hydrochloride obtained by reaction of lurasidone with one equivalent of hydrochloric acid. An atypical antipsychotic agent used for the treatment of schizophrenia.

Upstream product

• 14805-29-9 (3aR,4S,7R,7aS)?4,7?methylene?1H?isoindole?1,3(2H)-dione 
• 1421374-96-0 (3aR,7aR)-2,2-bis(2-hydroxyethyl)octahydro-1H-isoindolium mesylate 
• 23031-78-9 3-aminobenzisothiazole 
• 87691-87-0 3-(1-piperazinyl)-1,2-benzisothiazole 
• 1384511-83-4 3-[bis(hydroxyethyl)]amino-1,2-benzisothiazole 
• 14166-28-0 exo-bicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride 
• 173658-50-9 (1S,2S)-cyclohexane-1,2-dimethanol bis(methanesulfonate) 
• 3205-34-3 (1S,2S)-(–)-1,2-di(hydroxymethyl)cyclohexane 
• 542-92-7 cyclopenta-1,3-diene 
• 2746-19-2 (1R,2R,6S,7S)-4-oxa-tricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione 
• 186204-37-5 (3aR,7aR)-4’-(benzo[d]isothiazol-3-yl)octahydrospiro[isoindole-2,1’-piperazin]-2-ium methanesulfonate 
• 129-64-6 3,6-endomethylene-1,2,3,6-tetrahydrophthalic anhydride 
• 7647-01-0 hydrogenchloride 
• 194861-74-0 lurasidone 

Downstream Products

• 139563-25-0 (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl}hexahydro-1H-4,7-methanisoindol-1,3-dione dihydrochloride 

Relevant articles and documents

Method for preparing lurasidone and salt thereof

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.

Lurasidone key intermediate preparation method

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.

AN IMPROVED PROCESS FOR THE PREPARATION OF LURASIDONE BASE AND ITS SALT

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.

Preparation method for lurasidone hydrochloride

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.

Method for preparing lurasidone with high purity and high yield

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.

AN IMPROVED PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE

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.

PROCESS FOR THE INDUSTRIAL SYNTHESIS OF LURASIDONE

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.

PROCESS FOR LURASIDONE

The present invention provides a novel process for the purification of lurasidone substantially free of isomeric impurity.

PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE

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.

CRYSTALLINE LURASIDONE HYDROCHLORIDE

The present invention provides crystalline lurasidone hydrochloride, processes for its preparation, a pharmaceutical composition comprising it and its use for the treatment of schizophrenia.