Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Synthesis method of lansoprazole

A synthesis method and technology of lansoprazole, applied in the field of lansoprazole synthesis, can solve the problems of low total molar yield, excess metal elements of finished products, instability of lansoprazole and the like

Pending Publication Date: 2021-04-27
JIANGSU ZHONGBANG PHARMA +1
View PDF9 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In summary, the route has the following defects in the preparation of lansoprazole: the prepared lansoprazole is unstable and easily deteriorates in the drying process; the three wastes are many, and the cost of environmental protection is relatively high; the cost of using a vanadium-containing catalyst is relatively Higher, and there is a risk of excessive metal elements in the finished product; the route is long, the total molar yield is low, and the purity is low

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method of lansoprazole
  • Synthesis method of lansoprazole
  • Synthesis method of lansoprazole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] The preparation of Lansoprazole crude product

[0049] Add 272g of 2-mercaptobenzimidazole, 160g of drinking water and 160g of sodium hydroxide into a 5L reaction flask, and stir at room temperature until it dissolves. Prepare 500g lansoprazole chloride (also the 2-chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy) pyridine hydrochloride shown in II, following example The same as in ) and 2000g of drinking water solution. Add the aqueous solution of lansoprazole chloride dropwise to the reaction kettle at room temperature, and the dropwise addition time is 1 to 2 hours. After the drop is completed, stir and react at 10°C for 4 hours. Add the lye that 87g sodium hydroxide and 350g drinking water are made into, tetrabutylammonium bromide (TBAB) 17.5g. After finishing the addition, cool down to -10°C and start to drop 1887g of 10% sodium hypochlorite (in terms of available chlorine, that is, the oxidizing power of 1 gram of 10% sodium hypochlorite solution is equivalent to ...

Embodiment 2

[0053] The preparation of Lansoprazole crude product

[0054] Add 68g of 2-mercaptobenzimidazole, 40g of drinking water and 56g of potassium hydroxide into a 2L reaction flask, and stir at room temperature until dissolved. Prepare a solution of 125g lansoprazole chloride and 500g drinking water. Add the aqueous solution of lansoprazole chloride dropwise to the reaction kettle at room temperature for 1 to 2 hours. After the drop is completed, raise the temperature to 60° C. and stir for 1 hour. Cool down to 10°C and add lye made of 22g sodium hydroxide and 88g drinking water, and 8.4g trimethylbenzyl ammonium chloride. After the addition was completed, 472 g of 10% sodium hypochlorite aqueous solution was added dropwise at -10°C, and the dropwise addition time was about 2 hours. After the dropwise addition was completed, samples were taken and analyzed after the reaction at 0° C. for 2 hours, and the residual lansoprazole sulfide was ≤2.0%. A solution of 8.3 g of sodium thio...

Embodiment 3

[0058] The preparation of Lansoprazole crude product

[0059] Add 136g of 2-mercaptobenzimidazole, 80g of drinking water and 112g of potassium hydroxide into a 3L reaction flask, and stir at room temperature until it dissolves. Prepare the solution of 250g lansoprazole chloride and 1000g drinking water. Add the aqueous solution of lansoprazole chloride dropwise to the reaction kettle at room temperature for 1 to 2 hours. After the drop is completed, stir and react at 30°C for 2 hours. Add the lye that 62g potassium hydroxide and 170g drinking water are made into, 15.4g of tetrabutyl ammonium bisulfate. After the addition was completed, the temperature was lowered to -10°C and 944 g of 10% sodium hypochlorite aqueous solution was added dropwise, and the dropwise addition time was about 2 hours. After the dropwise addition was completed, the reaction was incubated at 25° C. for 1.5 h and then sampled for analysis. The residual lansoprazole sulfide was ≤2.0%. Prepare a solutio...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a synthesis method of lansoprazole, which comprises the following steps: condensing 2-mercaptobenzimidazole and 2-chloromethyl-3-methyl-4-(2, 2, 2-trifluoroethoxy) pyridine hydrochloride under alkaline conditions, oxidizing by a one-pot method to obtain a lansoprazole crude product, and finally refining to obtain the lansoprazole refined product. The method solves the problems that many three wastes are generated in lansoprazole production, a plurality of refining is needed, and drying deterioration is easily caused; the method is mild in reaction conditions, the total molar yield is 92% or above, the HPLC is 99.9% or above, and the method is suitable for industrial large-scale production.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, in particular to a synthetic method of lansoprazole. Background technique [0002] Lansoprazole (lansoprazole), chemical name 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]-sulfinyl]- 1H-benzimidazole, American Chemical Abstracts registration number CAS: 103577-45-3, structural formula as figure 1 . It is a proton pump inhibitor developed by Japan's Takeda Company, mainly used for gastric ulcer, duodenal ulcer, reflux esophagitis, and Zollinger-Ellison syndrome (gastrinoma). [0003] [0004] At present, there are many preparation methods for lansoprazole, but most of them have the disadvantages of low yield, high three wastes, poor drying stability and easy to lead to excessive impurities, and are not suitable for industrial production. [0005] What CN104530006 provides is a kind of " one pot method " method for preparing lansoprazole, promptly 2-mercaptobenzimidazole...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12
CPCC07D401/12
Inventor 黄双薛谊李维思陈莉张晓晴杨小波
Owner JIANGSU ZHONGBANG PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com