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Refining method and synthesis method of esomeprazole

A technology for esomeprazole sodium and a purification method is applied in the field of preparation of esomeprazole salts, which can solve the problems of easily causing adverse reactions, multiple impurities and the like, and achieves avoiding adverse reaction events, high purity and high optical purity. Effect

Active Publication Date: 2014-07-23
HEILONGJIANG ZBD PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] There are many kinds of synthetic methods of esomeprazole sodium, but most of them will produce more impurities in the preparation process. The control of process parameters, material proportioning, endpoint monitoring, and selection of refining methods are all key factors affecting product quality. If the purity of the product is low, it is easy to cause adverse reactions

Method used

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  • Refining method and synthesis method of esomeprazole
  • Refining method and synthesis method of esomeprazole
  • Refining method and synthesis method of esomeprazole

Examples

Experimental program
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Effect test

Embodiment 1

[0063] Example 1: Synthesis of Omeprazole Sulfide

[0064] First add 20L of ethanol (the amount is 8.70 times the volume of the weight of 2-mercapto-5-methoxy-1H-benzimidazole) into the reaction equipment, add 2.12kg (25.2mol) of sodium bicarbonate, after dissolving, add 2- Mercapto-5-methoxy-1H-benzimidazole 2.3kg (12.72mol), after dissolving, add 3,5-dimethyl-2-chloromethyl-4-methoxypyridine hydrochloride 2.8kg (12.56 mol), heat up to reflux reaction (TLC monitoring end point GF254 plate, developing solvent: ethyl acetate) until the raw material point disappears, adjust the pH value to neutrality with acetic acid, filter, and desolvate the filtrate under reduced pressure; add 10 L of dichloromethane to the residue After dissolving, wash with 2L×2 water (that is, use 2L water for 2 times), dry with anhydrous sodium sulfate, filter, and desolvate the filtrate under reduced pressure, add 8L xylene to stir and dissolve the material, add 100g activated carbon, stir for about 15mi...

Embodiment 2

[0065] Example 2: Synthesis of Omeprazole Sulfide

[0066] First, add 20L of methanol (the amount is 8.70 times the volume of the weight of 2-mercapto-5-methoxy-1H-benzimidazole) into the reaction equipment, add 1kg (25mol) of sodium hydroxide, and after dissolving, add 2-mercapto- 5-Methoxy-1H-benzimidazole 2.3kg (12.72mol), add 3,5-dimethyl-2-chloromethyl-4-methoxypyridine hydrochloride 2.8kg (12.56mol) after dissolution , heat up to the reflux reaction (TLC monitoring end point GF254 plate, developing solvent: ethyl acetate) until the raw material point disappears, adjust the pH value to neutrality with acetic acid, filter, and remove the filtrate under reduced pressure; after adding 10L of dichloromethane to dissolve the residue , washed with 2L × 2 water, dried with anhydrous sodium sulfate; filtered, the filtrate was desolvated under reduced pressure, and 8L of xylene was added to dissolve the material, then 100 g of activated carbon was added, stirred for about 15 min, ...

Embodiment 3

[0067] Example 3: Synthesis of Omeprazole Sulfide

[0068] First, add 20 L of methanol (the amount is 8.70 times the volume of the weight of 2-mercapto-5-methoxy-1H-benzimidazole) into the reaction equipment, add 2.6 kg (30.9 mol) of sodium bicarbonate, and after dissolving, add 2- Mercapto-5-methoxy-1H-benzimidazole 2.3kg (12.72mol), after dissolving, add 3,5-dimethyl-2-chloromethyl-4-methoxypyridine hydrochloride 2.8kg (12.56 mol), be warming up to reflux reaction (TLC monitoring GF254 plate, developing agent: petroleum ether and ethyl acetate, the volume ratio of the two is 1:6) to react to the disappearance of the raw material point, adjust the pH value to neutrality with acetic acid, filter, filtrate Precipitate under reduced pressure; add 10L of dichloromethane to dissolve the residue, wash with 2L×2 water, and dry with anhydrous sodium sulfate; filter, remove the filtrate under reduced pressure, add 8L of xylene to stir and dissolve the material, add 100g of activated c...

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Abstract

The invention relates to a refining method and a synthesis method of esomeprazole. The refining method comprises the following steps: firstly, suspending a crude esomeprazole product in 2-5 times of good organic solvents, stirring at low temperature, filtering to remove the impurities, slowly adding 10-20 times of adverse organic solvents, stirring to crystallize over night, and centrifuging to dry, thereby obtaining a refined esomeprazole product. The refining method of the esomeprazole is stable and controllable in process, simple and convenient to operate and easy to industrialize; the prepared esomeprazole is hihg in purity, high in yield, high in optical purity and stable in component, and happening of adverse reaction accidents is greatly avoided.

Description

technical field [0001] The invention relates to a preparation method of esomeprazole salt, in particular to a purification method of esomeprazole sodium and a synthesis method thereof. Background technique [0002] Omeprazole, the first proton pump inhibitor, has been used for more than ten years in the treatment of acid-related diseases. The drug has two optical isomers, a racemic mixture composed of S-omeprazole and R-omeprazole, of which S-omeprazole is also known as esoomeprazole, which is responsible for gastric acid secretion The inhibitory effect was significantly higher than that of single-dose omeprazole. [0003] Esomeprazole sodium (Esomeprazole sodium), S-omeprazole sodium, is a common esomeprazole salt, molecular formula: C 17 H 18 N 3 NaO 3 S, the appearance is white to light yellow powder, its chemical name is: 5-methoxy-2-((S)-((4-methoxy-3,5-dimethyl-2-pyridyl)methyl) base) sulfinyl)-1H-benzimidazole sodium, its chemical structure is: [0004] [0...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12
CPCC07D401/12
Inventor 方同华周广红董雪婷陈玉玲
Owner HEILONGJIANG ZBD PHARMA
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