- Preparation method of high-purity pramipexole dihydrochloride
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The invention provides a preparation method of high-purity pramipexole dihydrochloride, which comprises the following steps: (a) by using (S)-2-amino- 6-propionamido 4, 5, 6, 7-tetrahydrobenzothiazoleas a raw material and tetrahydrofuran as a solvent, reacting in the presence of a reducing agent, and adding diluted hydrochloric acid to terminate the reaction after the reaction is completed; (b) adding a sodium hydroxide solution to adjust the pH value, adding an extraction agent for extraction, adding an alcohol reagent, dropwise adding concentrated hydrochloric acid for salifying, cooling for crystallization, filtering and drying to obtain pramipexole dihydrochloride monohydrate; and (c) refining the pramipexole dihydrochloride monohydrate obtained in the step (b) through a ternary system of water, an alcohol reagent and an ester reagent, filtering and drying to obtain a pramipexole dihydrochloride finished product. The novel synthetic method of pramipexole dihydrochloride is simplein reaction steps, high in safety, high in yield, stable in water content and suitable for industrial production, and the purity of pramipexole dihydrochloride reaches 99.95% or above. The pramipexoledihydrochloride has stable water content and is suitable for industrial production.
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Paragraph 0027; 0030-0045
(2021/01/30)
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- A novel scalable synthesis of pramipexole
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Pramipexole is a dopamine D2 subfamily receptor agonist that is used for the treatment of Parkinsons disease. We report here on the successful application of the Fukuyama alkylation protocol to the development of a novel and scalable process for synthesis of pramipexole and its pharmaceutically acceptable salts. The synthesis consists of converting the crucial intermediate (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole to (6S)-N-(2-amino-4,5,6,7- tetrahydrobenzothiazole-6-yl)-2-nitrobenzenesulfonamide, which is in turn monoalkylated to (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-yl)-2-nitro- N-propylbenzenesulfonamide. Deprotection of the latter yields pramipexole base, which is finally converted to a crude pramipexole dihydrochloride monohydrate with a yield of over 50% over four steps. The process allows for the telescoping of the final three steps, has high conversion rates of intermediates, offers ease of purification, and preserves high optical purity throughout all of the stages.
- Zivec, Matej,Anzic, Borut,Gobec, Stanislav
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experimental part
p. 1125 - 1129
(2011/04/12)
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- PROCESSES FOR THE PREPARATION OF PRAMIPEXOLE AND SALTS THEREOF
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The invention relates to processes for the preparation of pramipexole or pharmaceutically acceptable salts thereof. More particularly, it relates to a process for the preparation of pramipexole dihydrochloride monohydrate. The invention also relates to a novel compound, 2-bromo-4-aminocyclohexanone and processes for its preparation. The 2- bromo-4-aminocyclohexanone is a useful intermediate in the preparation of pramipexole or salts thereof. The invention further relates to a single step process for the preparation of 2,6-diamino-4,5,6,7-tetrahydrobenzathiazole, an intermediate useful in the preparation of pramipexole or salts thereof.
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Page/Page column 12
(2008/12/07)
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- PROCESS FOR THE PREPARATION OF PRAMIPEXOLE BASE AND/OR ITS SALTS
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The process for the preparation of pramipexole base and/or its pharmaceutically accepted salts, especially hydrochloride salt, is based on the reaction of (S)-(-)2,6-diamino-4,5,6,7-tetrahydrobenzothiazole with an alkylating agent, wherein the reaction is carried out with the absence of a base, in a solvent from which the resulting N-monoalkylated product selectively precipitates out as a salt, which, after isolation from the reaction mixture: a) upon the treatment of inorganic base is converted into free pramipexole base, and then into another pharmaceutically accepted pramipexole salt, or b) is converted directly into another pharmaceutically accepted pramipexole salt or the hydrate thereof.
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Page/Page column 7
(2008/06/13)
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