(S)-pantoprazole sodium dihydrate and preparation method thereof

A technology for pantoprazole sodium and dihydrate, applied in the field of pharmaceutical synthesis, can solve the problems of large amount of non-polar crystallization solvent, unfavorable scale-up production, inability to complete crystallization, etc., achieves good appearance and color, and improves stability , the effect of stable quality

Inactive Publication Date: 2013-08-14
GUANGDONG HUANAN PHARMACEUTICAL GROUP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method is prone to oil formation when a non-polar solvent is added, and the amount of non-polar crystallization solvent required after the oil is formed is large. At the same time, due to the strong viscosity of the material, it is easy to adhere to the reaction equipment and stirring paddle, and cannot be completely crystallized. The resulting sodium salt has strong viscosity, which is unfavorable for industrialized scale-up production

Method used

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  • (S)-pantoprazole sodium dihydrate and preparation method thereof
  • (S)-pantoprazole sodium dihydrate and preparation method thereof
  • (S)-pantoprazole sodium dihydrate and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0050] Add 10g of highly enantioselective (S)-pantoprazole into a 250ml three-necked reaction flask, add 100ml of dichloromethane, dissolve completely under reflux, add activated carbon for decolorization for 30min, filter, and stir the filtrate at 20-30°C Add 10.0% by mass NaOH aqueous solution (prepared by NaOH and appropriate amount of purified water, the molar ratio of NaOH and (S)-pantoprazole is 1:1) to form salt and crystallize. =Stir and grow crystals at 0-10°C for 5 hours, filter, and vacuum-dry at 40-45°C for 6-8 hours to obtain 10.1 g of off-white (S)-pantoprazole sodium dihydrate, with a mass yield of 101.0%. Moisture: 8.9%, chemical purity: 99.82%, single impurity ≤ 0.1%; optical purity = 99.90%, dextrorotary body = 0.10%.

Embodiment 2

[0052] Add 10g of highly enantioselective (S)-pantoprazole into a 250ml three-necked reaction flask, add 100ml of dichloromethane, dissolve completely under reflux, add activated carbon for decolorization for 30min, filter, and stir the filtrate at 20-30°C Add 20.0% mass percentage of NaOH methanol solution (constituted by NaOH and appropriate amount of methanol, the molar ratio of NaOH and (S)-pantoprazole is 1.2:1) to form salt and crystallize, complete the addition within 10min, and put it in an ice-water bath T = Stir and grow the crystal at 0-10°C for 5 hours. Filtrate, and vacuum dry at 35-40°C for 6-8 hours to obtain 10.4 g of off-white (S)-pantoprazole sodium dihydrate, with a mass yield of 104.0%. Moisture: 8.8%, chemical purity: 99.85%, single impurity ≤ 0.1%; optical purity = 99.81%, dextrorotary body = 0.09%.

Embodiment 3

[0054] Add 10g of highly enantioselective (S)-pantoprazole into a 250ml three-necked reaction flask, add 100ml of dichloromethane, dissolve completely under reflux, add activated carbon for decolorization for 30min, filter, and stir the filtrate at 20-30°C Downstream add 10.0% mass percentage of CH 3 ONa methanolic solution (by CH 3 Configuration of ONa and appropriate amount of methanol, CH 3 The molar ratio of ONa and (S)-pantoprazole is 0.9:1) to form salt and crystallize. The addition is completed within 10 minutes, and the crystal is grown for 5 hours with stirring in an ice-water bath T=0-10°C. Filter and dry in vacuum at 20-25°C for 6-8 hours to obtain 10.1 g of off-white (S)-pantoprazole sodium dihydrate, with a mass yield of 101.0%. Moisture: 9.5%, chemical purity: 99.81%, single impurity ≤ 0.03%; optical purity = 99.84%, dextrorotary body = 0.16%.

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Abstract

The invention discloses a (S)-pantoprazole sodium dihydrate the chemically general name of which is (S)-5-difluoromethoxy-2[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole sodium dihydrate. The invention also discloses a preparation method of the (S)-pantoprazole sodium dihydrate. The preparation method comprises the step of cooperatively salifying and crystallizing at a proper temperature by using dichloromethane as a solvent and an alkaline compound of metal sodium as a salifying reagent, thereby obtaining the (S)-pantoprazole sodium dihydrate. The preparation method is simple to operate and mild in reaction condition; the prepared (S)-pantoprazole sodium dihydrate is good in appearance and color, high in purity and stable in quality when stored at room temperature; and industrial production scale can recur.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, in particular to (S)-pantoprazole sodium dihydrate and a preparation method thereof. Background technique [0002] Compound (S)-pantoprazole has a common chemical name of (S)-5-difluoromethoxy-2-[[(3,4-dimethoxy-2--pyridyl)methyl] Sulfyl]-1H-benzimidazole, (S)-pantoprazole and their pharmaceutically acceptable salts are described in CN1822835A. Pantoprazole is a proton pump inhibitor that inhibits the final step of gastric acid production by covalently binding to two sites of the H+-K+-ATPase system of gastric parietal cells in a dose-dependent manner and makes both basal and stimulated states gastric acid secretion is inhibited. (S)-Pantoprazole can be used as a proton pump inhibitor like esomeprazole for the treatment of diseases related to gastric acid secretion disorders such as: gastroesophageal reflux, gastritis, acute gastric mucosal lesions, gastric ulcer, compound acute gas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12
Inventor 谭珍友黄爱君邵广志
Owner GUANGDONG HUANAN PHARMACEUTICAL GROUP CO LTD
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