- A key intermediate for the preparation of ziprasidone
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The present invention relates to a ziprasidone key intermediate preparation method, wherein benzo[d]isothiazole-3-ol (or one) is adopted as a raw material, and reacts with a substituted sulfonyl chloride or anhydride under an alkaline condition to obtain benzo[d]isothiazole-3-substituted sulfonate, and the benzo[d]isothiazole-3-substituted sulfonate reacts with piperazine to prepare the ziprasidone key intermediate 3-(1-piperazinyl)-1,2-benzoisothiazole. The method of the present invention has characteristics of simple operation, easily available raw materials, less byproducts, simple post-treatment, less industrial three-waste and the like, and is especially suitable for industrial production.
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Paragraph 0119-0120
(2018/04/03)
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- Processes and intermediates for preparing 3-(1-piperazinyl)-1,2-benzisothiazole
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The present invention relates to processes for the preparation of 3-(1-piperazinyl)-1,2-benzoisothiazole or its pharmaceutically acceptable salt and to novel intermediates used in the process.
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- New disulfide route to 3-(1-piperazinyl)-1,2-benzisothiazole. Nucleus for atypical antipsychotic drugs
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A new, one-step commercial process for the preparation of 3-(1-piperazinyl)-l,2-benzisothiazole hydrochloride, a key intermediate for the syntheses of some new, "atypical antipsychotic" drugs, was developed. Reaction of bis(2-cyanophenyl) disulfide with excess piperazine at 120-140 °C for 3-24 h in the presence of small amounts of DMSO and 2-propanol formed 3-(l-piperazinyl)-l,2-benzisothiazole in 75-80% yields. The DMSO oxidized the liberated 2-mercaptobenzonitrile to regenerate bis(2-cyanophenyl) disulfide, thereby enabling the utilization of both halves of the symmetrical disulfide to generate product. The reaction mechanism for the conversion of the bis(2-cyanophenyl) disulfide to 3-amino-1,2-benzisothiazole involves the formation of ring-opened sulfenamide and benzamidine intermediates and then their subsequent ring closure to regenerate the 1,2-benzisothiazole nucleus. A safe, efficient, and robust process to prepare 3-(l-piperazinyl)-1,2-benzisothiazole under very concentrated reaction conditions was developed and successfully scaled up in the pilot plant to support the development of ziprasidone.
- Walinsky, Stanley W.,Fox, Darrell E.,Lambert, John F.,Sinay, Terry G.
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p. 126 - 130
(2013/09/08)
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- PRO-DRUGS OF 5-(2-(4-(1,2-BENZISOTHIAZOL-3-YL)-1-PIPERAZINYL)ETHYL)-6-CHLORO-1,3-DIHYDRO-2H-INDOL-2-ONE
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The present invention relates to a pro-drug of ziprasidone or pharmaceutically acceptable salts thereof, processes for its preparation, and pharmaceutical compositions and methods of treatment comprising said pro-drug.
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- Pro-drugs of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloro-1,3-dihydro-2h-indol-2-one
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The present invention relates to a pro-drug of ziprasidone or pharmaceutically acceptable salts thereof, processes for its preparation, and pharmaceutical compositions and methods of treatment comprising said pro-drug.
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- 1,2,4-TRIAZOL-3-ONE ANTIDEPRESSANTS
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Phenoxyalkyl substituted-1,2,4-triazolones having anti-depressant properties typified by 2-3-4-(3-chlorophenyl)-1-piperazinyl!propyl!-5-ethyl-4-(2-phenoxyethyl)-2H-1,2, 4-triazol-3(4H)-one are disclosed.
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- Benzisothiazole and benzisoxazole piperazine derivatives
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Disubstituted N,N-piperazinyl derivatives are disclosed wherein one substituent is benzisothiazol-3-yl or benzisoxazol-3-yl and the other is alkylene attached to heterocycles such as azaspiro[4.5]decanedione, dialkylglutarimide, thiazolidinedione and spirocyclopentylthiazolidinedione or butyrophenone-like groups. The compounds have psychotropic properties and 8-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-8-azaspior[4.5]decane-7,9-dione is a typical embodiment having selective antipsychotic activity.
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