Novel preparation method of esprazole magnesium trihydrate and intermediate thereof

Abstract

The invention relates to a novel preparation method of esprazole magnesium trihydrate and an intermediate thereof, and belongs to a pharmaceutical technology. The preparation method comprises the following steps: (1) performing condensation reaction to prepare omeprazole sulfide; and (2) performing chiral oxidation reaction to prepare esprazole, performing potassium salt forming reaction to prepare esprazole potassium, and performing ion exchange reaction to obtain the esprazole magnesium trihydrate. The method is high in product yield, high in product purity, mild and safe in reaction condition, low in energy consumption, easy to control and suitable for industrial mass production.

Description

technical field [0001] The invention relates to chemical medicine synthesis technology, in particular to a new preparation method of esomeprazole magnesium trihydrate and its intermediate. Background technique [0002] Esomeprazole magnesium trihydrate, chemical name: bis-S-5-methoxy-2{[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl ]sulfinyl}-1H-benzimidazole magnesium trihydrate. Molecular formula is C 34 h 36 MgN 6 o 6 S 2 ·3H 2 O, molecular weight 767.1, indication for gastroesophageal reflux disease, combined with appropriate antibiotics can eradicate Helicobacter pylori. Because of its good medicinal performance and convenient route of administration, it is favored in clinical use. [0003] The synthetic route generally includes the ion exchange reaction between the intermediate esomeprazole sodium salt or potassium salt and magnesium salt; the purity and yield of the finished product depend on the reaction conditions used in the synthetic route, the reagents used an...

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Problems solved by technology

Disclosed a kind of preparation method of esomeprazole magnesium as CN104803978A, wherein the required temperature control range of each step is from-20 degree centigrade to reflux temperature, under the situation of mass production, there is difficulty in the control of its reaction process, it is difficult to obtain as its The purity yield of data record; CN104447699A also discloses a kind of preparation method of esomeprazole magnesium trihydrate, and its required maximum reaction temperature needs to reach 70 degrees Celsius, and the required temperature control range is at 0-70 degrees Celsius Between, there is also difficulty in the control of the reaction process; and acetonitrile is added in the refining and purification of the intermediate potassium salt, and heated to 60-65 degrees Celsius and stirred for 2.5 hours, but acetonitrile is volatile, toxic, and flammable, and there are potential safety hazards

According to the disclosure of this patent application, 4L of acetonitrile is required for the preparation of 0.8 kg of esomeprazole potassium; if this ratio is used for mass production, a large amount of acetonitrile will be consumed in the production process; in addition, some steps of the method require up to 70 degrees Celsius It can be expected that potential safety hazards will easily escalate, and it will pollute the environment and pose a threat to the health of personnel in the production environment.

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