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

Clopidogrel bisulfate impurity A and preparation method thereof

A technology of clopidogrel bisulfate and hydroxymethyl clopidogrel, applied in organic chemistry methods, organic chemistry, etc.

Pending Publication Date: 2022-01-04
CHENGDU ORGANOCHEM CO LTD
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] The object of the present invention is to provide a new clopidogrel bisulfate impurity A, the discovery of this impurity is beneficial to the content control of the clopidogrel bisulfate impurity compound, thereby solving the structural problem of the impurity in the small polar region of clopidogrel , which can provide sufficient theoretical support and material basis for the research on impurities of raw materials and the formulation of quality standards for raw materials

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
  • Clopidogrel bisulfate impurity A and preparation method thereof
  • Clopidogrel bisulfate impurity A and preparation method thereof
  • Clopidogrel bisulfate impurity A and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] A kind of preparation method of clopidogrel bisulfate impurity A provided by the embodiment of the present invention comprises the following steps:

[0047] 1. Preparation of hydroxymethylclopidogrel impurity Z1:

[0048] 1.1 Take an appropriate amount of hydrochloric acid and a 250ml three-necked flask, take an appropriate amount of concentrated sulfuric acid and add it to a constant pressure dropping funnel, and slowly add it dropwise to the hydrochloric acid. In the three-necked bottle of methyl chloride, absorb to saturation, seal it for use;

[0049] 1.2 Take another 500ml three-neck bottle, accurately weigh the condensate hydrochloride (38.72g, 1eq), paraformaldehyde (19.95g, 6.0eq), formic acid (1.61g, 0.31eq), configure a thermometer, magnetic stirring device, reflux device, add the methylene chloride solution that absorbs hydrogen chloride gas to saturation in 1.1, seal the reaction, reflux at 40°C, reflux temperature is 37°C, and reflux time is 48 hours, stop...

Embodiment 2

[0058] A kind of preparation method of clopidogrel bisulfate impurity A provided by the embodiment of the present invention comprises the following steps:

[0059] 1. Preparation of hydroxymethylclopidogrel impurity Z1:

[0060] 1.1 Take an appropriate amount of hydrochloric acid and a 250ml three-necked flask, take an appropriate amount of concentrated sulfuric acid and add it to a constant pressure dropping funnel, and slowly add it dropwise to the hydrochloric acid. In the three-necked bottle of methyl chloride, absorb to saturation, seal it for use;

[0061] 1.2 Take another 500ml three-neck bottle, accurately weigh the condensate hydrochloride (38.72g, 1eq), paraformaldehyde (19.95g, 6.0eq), formic acid (1.61g, 0.31eq), configure a thermometer, magnetic stirring device, reflux device, add the methylene chloride solution that absorbs hydrogen chloride gas to saturation in 1.1, seal the reaction, reflux at 40°C, reflux temperature is 37°C, and reflux time is 48 hours, stop...

Embodiment 3

[0066] A kind of preparation method of clopidogrel bisulfate impurity A provided by the embodiment of the present invention comprises the following steps:

[0067] 1. Preparation of hydroxymethylclopidogrel impurity Z1:

[0068] 1.1 Take an appropriate amount of hydrochloric acid and a 250ml three-necked flask, take an appropriate amount of concentrated sulfuric acid and add it to a constant pressure dropping funnel, and slowly add it dropwise to the hydrochloric acid. In the three-necked bottle of methyl chloride, absorb to saturation, seal it for use;

[0069] 1.2 Take another 500ml three-neck bottle, accurately weigh the condensate hydrochloride (38.72g, 1eq), paraformaldehyde (19.95g, 6.0eq), formic acid (1.61g, 0.31eq), configure a thermometer, magnetic stirring device, reflux device, add the methylene chloride solution that absorbs hydrogen chloride gas to saturation in 1.1, seal the reaction, reflux at 40°C, reflux temperature is 37°C, and reflux time is 48 hours, stop...

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 clopidogrel bisulfate impurity A and a preparation method thereof. The structural formula of the impurity A is shown in the specification. The preparation method comprises the following steps of: (1) carrying out a reaction on condensation compound hydrochloride, paraformaldehyde and formic acid in a DCM solvent, the generated product clopidogrel reacting under an acidic condition to form a hydroxymethyl clopidogrel impurity; (2) after the reaction is completed, washing with water, adjusting with a sodium bicarbonate solution, separating liquid to retain an organic phase, and performing vacuum concentration, separation and purification to obtain an impurity Z1; and (3) reacting the impurity Z1 prepared in the step (2) with Z1-SM1, HATU and triethylamine in a DMF solvent, then adding water and EA for extraction, and performing rotary evaporation on an organic phase, separation and purification to obtain the impurity A. The clopidogrel bisulfate impurity A provided by the invention is a brand-new compound. The structure problem of clopidogrel small-polarity region impurities is solved through structure confirmation and synthesis of the impurity, and sufficient theoretical support and research material basis can be provided for bulk drug impurity research and bulk drug quality standard establishment.

Description

technical field [0001] The invention relates to the technical field of impurities in medicinal chemistry and their preparation, in particular to a clopidogrel bisulfate impurity A and a preparation method. Background technique [0002] Clopidogrel is a common antiplatelet aggregation drug that inhibits the binding of adenosine diphosphate to platelet receptors and inhibits platelet aggregation. Platelet aggregation is an important part of atherosclerosis, and inhibition of platelet aggregation can effectively prevent thrombosis. Therefore, clopidogrel has a broad market prospect and has attracted extensive attention from the pharmaceutical industry. [0003] Clopidogrel reports three kinds of impurities in Chinese Pharmacopoeia, impurity Ⅰ: [0004] [0005] C 15 h 15 Cl 2 NO 2 S 344.26 [0006] (+) 2-[S-(2-chlorophenyl)]-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)acetic acid hydrochloride [0007] Impurity Ⅱ: [0008] [0009] [0010] C 16 h 17 Cl ...

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
IPC IPC(8): C07D495/04
CPCC07D495/04C07B2200/07
Inventor 王利民谈平忠邓倩郑守军
Owner CHENGDU ORGANOCHEM 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