186204-37-5

Basic information

• Product Name: (3aR,7aR)-4'-(1,2-Benzisothiazol-3-yl)octahydrospiro[2H-isoindole-2,1'-piperaziniuM] Methanesulfonate
• Synonyms: (3aR,7aR)-4'-(1,2-Benzisothiazol-3-yl)octahydrospiro[2H-isoindole-2,1'-piperaziniuM] Methanesulfonate;4-(Benzo[d]isothiazol-3-yl)-1-((3aR,7aR)-hexahydro-1H-isoindol-2(3H)-yl)piperazin-1-iuM-1-sulfonate;(3aR,7aR), octahydro-[2H-isoindole-2-spiro-1'-piperazinium], 4'-(1,2-benzisothiazol-3-yl), methanesulfonate (1:1);4-(1,2-Benzothiazol-3-yl)-1-[(3aR,7aR)-octahydro-2H-isoindol-2-yl]piperazin-1-ium-1-sulfonate;Spiro[2H-isoindole-2,1'-piperazinium], 4'-(1,2-benzisothiazol-3-yl)octahydro-, (3aR,7aR)-, methanesulfonate (1:1);(3aR,7aR)-4'-(Benzo[d]isothiazol-3-yl)octahydrospiro[isoindole-2,1'-piperazin]-1'-ium methanesulfonate;(3aR,7aR)-4'-(benzo[d]isothiazol-3-yl)octahydrospiro[isoindole- 2,1'-piperazin]-2-ium methanesulfonate
• CAS NO: 186204-37-5
• Molecular Formula: C19H26N4O3S2
• Molecular Weight: 422.56474
• Mol File: 186204-37-5.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: (3aR,7aR)-4'-(1,2-Benzisothiazol-3-yl)octahydrospiro[2H-isoindole-2,1'-piperaziniuM] Methanesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: (3aR,7aR)-4'-(1,2-Benzisothiazol-3-yl)octahydrospiro[2H-isoindole-2,1'-piperaziniuM] Methanesulfonate(186204-37-5)
• EPA Substance Registry System: (3aR,7aR)-4'-(1,2-Benzisothiazol-3-yl)octahydrospiro[2H-isoindole-2,1'-piperaziniuM] Methanesulfonate(186204-37-5)

Safety Data

• Hazardous Substances Data: 186204-37-5(Hazardous Substances Data)

Usage

Uses

(3aR,7aR)-4''-(1,2-Benzisothiazol-3-yl)octahydro-spiro[2H-isoindole-2,1''-piperazinium] Methanesulfonate (B197865) is a useful synthetic intermediate for Lurasidone Hydrochloride (L474920), an antipsychotic used for treatment of schizophrenia.

InChI:InChI=1S/C19H26N4O3S2/c24-28(25,26)23(22-13-15-5-1-2-6-16(15)14-22)11-9-21(10-12-23)19-17-7-3-4-8-18(17)27-20-19/h3-4,7-8,15-16H,1-2,5-6,9-14H2/t15-,16-/m0/s1

Upstream product

• 186204-35-3 (1R,2R)-(-)-trans-cyclohexane-1,2-diylbis(methylene)dimethanesulfonate 
• 87691-88-1 3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride 
• 133070-64-1 3-(piperazin-1-yl)-1,2-benzisothiazole hydrochloride 
• 87691-87-0 3-(1-piperazinyl)-1,2-benzisothiazole 

Downstream Products

• 1260022-13-6 N-{[(1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl)-piperazin-1-yl]methyl}cyclohexyl]methyl}biphenyl-3-sulfonamide 
• 139563-25-0 lurasidone hydrochloride 
• 367514-88-3 (3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(l1,2-benzisothiazol-3-yl)piperazin-1-yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7-methanisoindol-1,3-dione hydrochloride 
• 194861-74-0 [14C]-Lurasidone 
• 194861-74-0 lurasidone 

Relevant articles and documents

Preparation method of lurasidone

The invention relates to a preparation method of lurasidone. The preparation method comprises the following steps of: reacting a compound as shown in a formula (I) with a compound as shown in a formula (II) under the action of an organic solvent A and a catalyst A, and performing quenching with a weak base solution to obtain a lurasidone crude product. According to the preparation method, the organic solvent A is selected from N-methyl pyrrolidone, N, N-dimethylformamide or a mixture of N-methyl pyrrolidone and N, N-dimethylformamide, preferably N-methyl pyrrolidone; the catalyst A is cesium carbonate; the weak base solution is selected from a cesium carbonate solution, a potassium carbonate solution or a sodium carbonate solution, preferably the potassium carbonate solution. The method is simple to operate, high in product yield, short in reaction time, low in cost and suitable for actual industrial production.

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.

DEUTERATED LURASIDONE

This invention relates to deuterated forms of hexahydro-4,7-methano-1H-isoindole-1,3(2H)-diones, and pharmaceutically acceptable salts thereof. In one aspect, the invention provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof. This invention also provides compositions comprising a compound of this invention, including pharmaceutical compositions comprising the compound and a pharmaceutically acceptable carrier. This invention also provides the use of such compounds and compositions in methods of treating diseases and conditions that are beneficially treated by administering a compounds that modulates the activity of a receptor selected from the group consisting of central dopamine Type 2 (D2) receptor and serotonin Type 2 (5HT2A) receptor. Some exemplary embodiments include a method of treating a disease or condition selected from schizophrenia and depressive episodes associated with bipolar I disorder, the method comprising the step of administering to a subject in need thereof a pharmaceutically acceptable composition of the present invention.

A process for the preparation of intermediates [...] (by machine translation)

The invention relates to a process for the preparation of intermediates [...], the intermediate body is (3aR, 7aR) - 4 ˊ - (1,2-benzisothiazol-3-yl) eight hydrogen spiral [2H-isoindole -2,1 ˊ-piperazine] a sulfonate. The (1R, 2R) - 1,2-cyclohexane dimethanol as raw materials, dialkyltinacetal after armor is a sulfonic acid ester, with the 3 - (1-piperazinyl) - 1,2 benzothiazin hydrochloride reaction to obtain the required intermediate. (by machine translation)

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 THE PREPARATION OF LURASIDONE HYDROCHLORIDE

Provided herein is a process for the preparation of the antipsychotic agent lurasidone hydrochloride useful for the treatment of schizophrenia.

PROCESS FOR THE PREPARATION OF LURASIDONE HYDROCHLORIDE

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.

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.