Method for purifying esomeprazole sodium

A technology of esomeprazole sodium and a purification method, which is applied in the field of purification of esomeprazole sodium, can solve the problems of not specifying too much the specific content of residual solvents, difficulty in removing residual solvents, and no mention of residual solvents, etc. Achieve the effect of low cost, high yield and high enantiomeric purity

Active Publication Date: 2013-05-08
四川尚锐生物医药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there are many reports on the synthesis methods of esomeprazole sodium, such as US2007 / 0259921 A1 methanol and acetone co-distillation crystallization, or ethyl acetate as solvent crystallization; WO2008 / 152462 A1, WO2009 / 47775 A2, US2010 / 125142 A1 Ethyl acetate crystallization; WO2010 / 58409 A2, CN101323609 A, CN102633776 A all disclose the synthesis method of esomeprazole sodium, the yield, purity and enantiomeric purity in the synthesis are all high, but for the residual None of the solvents are mentioned, and the specific content of residual solvents is not stated too much
CN102089296 A and EP2143722 A1 disclose a method for preparing esomeprazole sodium crystal form by recrystallization in a methanol solvent, and the obtained esomeprazole sodium sample contains about 10% of methanol (w / w ), and to reduce the methanol content to 0.5%, it needs to be blown with water-saturated nitrogen at 40°C for at least 6 hours, and then vacuum-dried at 35°C for 10-16 hours, and repeated at least twice. It can be seen that the removal of residual solvents is quite difficult and complicated

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  • Method for purifying esomeprazole sodium
  • Method for purifying esomeprazole sodium

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Experimental program
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Effect test

Embodiment 1

[0030] Weigh 3.0 kg of crude esomeprazole sodium, add 9.0 L of methanol, heat to dissolve at 65±5°C, add 0.1 kg of activated carbon for decolorization for 10 min, heat filter, add 0.03 kg of esomeprazole sodium seed crystals, wait After the system is turbid, add 9.0L of isopropyl ether, cool down to 0±5°C, continue to stir for 1h, filter, add 2.5L of acetone to the filter cake, stir and dissolve at room temperature, and when the system is cloudy, add 2.5L of isopropyl ether, filter, and filter the cake Vacuum-dried to obtain 2.5 kg of esomeprazole sodium refined product. After HPLC detection, the content is 99.5%, the largest single impurity is 0.03%, the total impurity is 0.06%, and the enantiomeric purity is 99.9%.

Embodiment 2

[0032] Weigh 3.0 kg of crude esomeprazole sodium, add 12.0 L of ethanol, heat to dissolve at 65±5°C, add 0.1 kg of activated carbon for decolorization for 10 min, heat filter, add 0.03 kg of esomeprazole sodium seed crystals, wait After the system is turbid, add 9.0L of isopropyl ether, cool down to 0±5°C, continue to stir for 1h, filter, add 2.5L of acetone to the filter cake, stir and dissolve at room temperature, and when the system is cloudy, add 2.5L of isopropyl ether, filter, and filter the cake Vacuum-dried to obtain 2.3 kg of esomeprazole sodium refined product. After HPLC detection, the content is 99.7%, the largest single impurity is 0.02%, the total impurity is 0.07%, and the enantiomeric purity is 99.8%.

Embodiment 3

[0034]Weigh 3.0 kg of crude esomeprazole sodium, add 9.0 L of methanol, heat to dissolve at 65±5°C, add 0.1 kg of activated carbon for decolorization for 10 min, heat filter, add 0.03 kg of esomeprazole sodium seed crystals, wait After the system is turbid, add 9.0L of isopropyl ether, cool down to 0±5°C, continue to stir for 1h, filter, add 1.5L of acetone to the filter cake, stir and dissolve at room temperature, and when the system is cloudy, add 3.0L of isopropyl ether, filter, and filter the cake Vacuum-dried to obtain 2.5 kg of esomeprazole sodium refined product. After HPLC detection, the content is 99.2%, the largest single impurity is 0.04%, the total impurity is 0.09%, and the enantiomeric purity is 99.7%.

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Abstract

The invention relates to a method for purifying esomeprazole sodium, which comprises the following steps: after dissolving an esomeprazole sodium crude product in 0.5-10 times of an alcohol solvent, adding a poor solvent, filtering to obtain a solid, dissolving the solid in 0.5-10 times of acetone, crystallizing until the system becomes turbid, adding a poor solvent, filtering, and drying to finally obtain the sample. The method can remove abundant residual solvents which can not be easily removed in the prior art to obtain the high-purity low-solvent-residue high-yield product, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, in particular to a method for purifying esomeprazole sodium. Background technique [0002] Esomeprazole sodium is the sodium salt form of esomeprazole, a proton pump inhibitor with the following structure: [0003] [0004] Esomeprazole is the S-isomer of omeprazole, which is the first isomer proton pump inhibitor available for clinical intravenous administration in the world, and has a stronger effect. Preclinical tests have shown that esomeprazole’s anti-acid secretion, anti-ulcer effects and anti-Helicobacter pylori activity are significantly stronger than omeprazole; clinical trials have shown that esomeprazole sodium’s acid-suppressing effect is significantly stronger than that of omeprazole Larazole, Lansoprazole, and Pantoprazole. At the same time, the safety of esomeprazole sodium is also relatively good, no teratogenic and mutagenic effects have been seen in preclinical tests, and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12
Inventor 刘超吴昆叶子峥彭显峰戴萍
Owner 四川尚锐生物医药有限公司
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