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

A kind of process improvement method of preparing pioglitazone hydrochloride

A technology for pioglitazone hydrochloride and process improvement, applied in the field of thiazolidinedione drug pioglitazone hydrochloride, can solve the problems of low yield of imine compounds, poor refining effect, many reaction by-products, etc., and achieves easy post-processing operation and hydrogenation. The effect of high yield and improved purity

Active Publication Date: 2015-09-09
ZHEJIANG HUAHAI PHARMA CO LTD
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are many disadvantages in this method: Meerwein is very difficult to control in production, because the reaction process is exothermic and N2 is released during the process, which may cause danger; there are many by-products in the Meerwein reaction, and it is difficult to refine; the acrylate used in the raw material has a foul smell, and the operation Special protection is required; waste liquid with metals is treated; the yield of imine compounds is extremely low
[0017] However, the inventors have found through experimental research that the refining effect of compound (III) by forming hydrochloride is not good, resulting in the compound (III) being brought into the finished product to exceed the standard; and the single impurity produced by the reduction process of compound (III) passes through Still more than 0.15% after refining

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
  • A kind of process improvement method of preparing pioglitazone hydrochloride
  • A kind of process improvement method of preparing pioglitazone hydrochloride
  • A kind of process improvement method of preparing pioglitazone hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Preparation of (5-[[4-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl]methylene]-2,4-thiazoledione mesylate (IV):

[0034] 27.2 g of 5-[[4-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl]methylene]-2,4-thiazoledione (III) (HPLC purity: 96.1 %), methanesulfonic acid 7.74g and ethanol 136ml were added in the 250ml reaction flask, heated to reflux for 1 hour, cooled, filtered and dried to obtain 32.5g of white solid (IV).

[0035] Yield 95%, HPLC purity: 99.5%.

Embodiment 2

[0037] The preparation of pioglitazone hydrochloride (I):

[0038] Put 10g of the white solid (IV) obtained in Example 1, 50ml of glacial acetic acid, and 1.3g of 7% Pd / C (dry) into the hydrogenation kettle, empty the air, fill in hydrogen, and pressurize to 8-10kg / cm 2 , heated to 95 ° C under the condition of catalytic hydrogenation for 48 hours. The palladium carbon was removed by filtration, and the palladium carbon was washed with a small amount of glacial acetic acid, and the filtrates were combined and concentrated to obtain an oil. Add 100ml of water, stir to precipitate a white solid, and filter. The white solid obtained by filtration was adjusted to a pH value of about 7-9 with 25% concentrated ammonia water, filtered and dried to obtain 7.4 g of pioglitazone with a yield of 93.5%. Add 4 g of 30% ethanol hydrochloric acid solution and 105 ml of ethanol to the obtained pioglitazone, heat to reflux until completely dissolved, cool and precipitate to obtain a white so...

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 an improved technological method for preparing pioglitazone hydrochloride. On one hand, 5-[[4-[2-(5-ethyl-2-pyridyl) ethyoxyl] phenyl] methylene]-2, 4-thiazolidinedione (III) is used for forming new intermediate compound, i.e. mesylate as shown in a formula (III), to reach the goal of refining (III); and on the other hand, the mesylate as shown in the formula (III) is used as raw material for hydrogenation, and the pioglitazone hydrochloride can be obtained through hydrogenation, liberation by adding alkaline and acidification by hydrochloric acid. The invention has the advantages of mild hydrogenation conditions, thorough hydrogenation, high product purity and the like.

Description

technical field [0001] The invention relates to a process improvement method of pioglitazone hydrochloride, a thiazolidinedione drug. Background technique [0002] Pioglitazone hydrochloride is a thiazolidinedione compound (TZD), which belongs to insulin sensitizer and is used for the treatment of type II diabetes. Its structural formula is as follows: [0003] [0004] Pioglitazone hydrochloride and its preparation method have been reported in Chinese patent CN1003934B, and its route is as follows, [0005] [0006] The method is to diazotize the amine compound and react with acrylate under the action of a copper catalyst, that is, the so-called Meerwein aromatization reaction to obtain a halogenated ester, and react the halogenated ester with thiourea to obtain an imine compound; the imine compound is hydrolyzed to obtain obtain the target product. There are many disadvantages in this method: Meerwein is very difficult to control in production, because the reactio...

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 Patents(China)
IPC IPC(8): C07D417/12
Inventor 芦启锋刘创伟甘立新罗兰庆
Owner ZHEJIANG HUAHAI PHARMA CO LTD
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