- A Simple and Commercially Viable Process for Improved Yields of Metopimazine, a Dopamine D2-Receptor Antagonist
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An efficient, practical, and commercially viable manufacturing process was developed with ≥99.7% purity and 31% overall yield (including four chemical reactions and one recrystallization) for an active pharmaceutical ingredient, called Metopimazine (1), an antiemetic drug used to prevent emesis during chemotherapy. The development of two in situ, one-pot methods in the present synthetic route helped to improve the overall yield of 1 (31%) compared with earlier reports (15%). For the first time, characterization data of API (1), intermediates, and also possible impurities are presented. The key process issues and challenges were addressed effectively and achieved successfully.
- Karicherla, Venumanikanta,Phani, Kumar,Bodireddy, Mohan Reddy,Prashanth, Kumar Babu,Gajula, Madhusudana Rao,Pramod, Kumar
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- New process for preparing metopimazine
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The invention discloses a new process for preparing metopimazine. The new process comprises the following steps: in a reactor, using o-fluorothiophenol and 1-chloro-4-(methylsulphonyl)-2-nitrobenzeneas raw materials to react in acetone to obtain 2-(2-fluorophenyl thio)-5-(methylsulfonyl) nitrobenzene; then adding ethanol and ferric chloride for a heating reaction to generate 2-(2-fluorophenyl thio)-5-(methylsulfonyl) aniline; adding dimethyl sulfoxide, adding NaH, heating for reaction, cooling to a room temperature, adding water, and stirring to prepare 2-methylsulfonyl-10H-phenothiazine; then adding 10-acetyl-2-methylsulfoxide-10H phenothiazine and potassium hydroxide to react to prepare 10-acetyl-2-methylsulfonyl-(5-sulfoxide)-10H phenothiazine; adding acetone, carrying out concentration and extraction to obtain a methylene chloride solution of 10-acetyl-2-methylsulfonyl-10H phenothiazine; adding piperidine-4-formamide after the temperature is lowered; adding sodium borohydride acetate; carrying out reaction and filtration; and pulping filter cakes to obtain metopimazine. According to the new process provided by the invention, the final yield is greatly improved by optimizing the reaction route and reaction conditions, and the product purity reaches 99.3% or higher.
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- Stable freeze-dried pharmaceutical formulation
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The subject of the invention is a freeze-dried formulation consisting of an amorphous phase and a crystalline phase, which is pharmaceutically acceptable, comprising at least one nonprotein active ingredient, characterized in that it contains mannitol and alanine in a ratio R of between 0.1 and 1, R representing the mass of mannitol to the mass of alanine.
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