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

Impurity compound of Nintedanib, as well as preparation method, application and detection method of impurity compound

A technology of nintedanib and its compounds, which is applied in the field of medicinal chemistry, can solve the problems of public reporting without impurities and achieve the effect of improving quality standards

Inactive Publication Date: 2017-05-31
REYOUNG PHARMA
View PDF2 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] At present, there is no public report of this impurity in domestic and foreign literature

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
  • Impurity compound of Nintedanib, as well as preparation method, application and detection method of impurity compound
  • Impurity compound of Nintedanib, as well as preparation method, application and detection method of impurity compound
  • Impurity compound of Nintedanib, as well as preparation method, application and detection method of impurity compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Add 3-[methoxy(phenyl)methylene]-2-oxoindoline-6-carboxylic acid methyl ester (8.8g, 28mol) and piperidine (4.8g, 57mmol) into methanol 80mL , The reaction was stirred at 60°C, and the reaction was completed in 2 to 5 hours. The reaction solution was cooled, and a solid precipitated out. The solid was filtered and rinsed with methanol to obtain 8.5 g of an impurity compound as a yellow solid.

[0053] HPLC detection, product purity 97.1%.

[0054] The HPLC method is: take 5 mg of the impurity compound, add it to a 25 mL volumetric flask, and use an appropriate amount of mobile phase A-mobile phase B (45:55) to sonicate to dissolve and dilute to the mark as the test solution.

[0055] The chromatographic conditions are:

[0056] (1) Chromatographic column: octadecylsilane bonded silica gel.

[0057] (2) Mobile phase: mobile phase A is 20mmol / L potassium dihydrogen phosphate solution (adjust pH value to 3.0 with phosphoric acid), mobile phase B is acetonitrile, and car...

Embodiment 2

[0062]Methyl N-acetyl-3-[methoxy(phenyl)methylene]-2-oxoindoline-6-carboxylate (10 g, 28 mmol) and piperidine (4.8 g, 57 mmol) Add 40mL of methanol and 10mL of N,N-dimethylformamide, and reflux at 68°C to complete the reaction in 4 to 7 hours. The reaction solution was cooled, added with 100 mL of water, extracted with 80 mL of dichloromethane, washed with 50 mL of saturated sodium chloride solution x 2. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was distilled under reduced pressure. The residue was crystallized by adding 30 mL of methanol to obtain 8.1 g of the impurity compound as a yellow solid. HPLC detection showed that the purity of the impurity compound was 98.46%.

Embodiment 3

[0064] Methyl N-chloroacetyl-3-[methoxy(phenyl)methylene]-2-oxoindoline-6-carboxylate (10 g, 28 mmol) and piperidine (4.8 g, 57 mmol ) into 30 mL of N,N-dimethylformamide, react at 80°C, and complete the reaction in 2 to 4 hours. The reaction solution was cooled, added with 100 mL of water, extracted with 100 mL of dichloromethane, and washed with 50 mL of saturated sodium chloride solution x 3. The organic phase was dried over anhydrous sodium sulfate, filtered, and dichloromethane was distilled off from the filtrate under reduced pressure. The residue was crystallized by adding 50 mL of isopropanol, and filtered to obtain 7.4 g of an impurity compound as a yellow solid. HPLC detection showed that the purity of the impurity compound was 99.13%.

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

PropertyMeasurementUnit
purityaaaaaaaaaa
Login to View More

Abstract

The invention relates to an impurity compound of Nintedanib, as well as a preparation method, application and detection method of the impurity compound. The structure of the impurity compound is shown in the following formula I (as shown in the specification), or in the following formula II (as shown in the specification). The invention aims to improve the quality standard of Nintedanib through study on impurities to guarantee the safe medication of Nintedanib. According to the preparation method disclosed by the invention, the pure impurity compound of Nintedanib is obtained, so that a reference substance for qualitative and quantitative analysis is provided for the detection of a finished Nintedanib product.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to an impurity compound of nintedanib, a preparation method, an application and a detection method thereof. [0002] technical background [0003] Nintedanib Esylate was developed by Boehringer Ingelheim and was approved by the US Food and Drug Administration (FDA) on October 15, 2014, and then approved in Europe on November 21, 2014. The Drug Administration (EMA) approved the marketing, and then was approved by the Japanese Medicines and Medical Devices Administration (PMDA) on July 3, 2015, and was marketed by Boehringer Ingelheim. [0004] NintedanibEsylate is a multiple tyrosine kinase inhibitor that works by inhibiting growth factor receptors associated with the pathogenesis of idiopathic pulmonary fibrosis (IPF). It has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) and non-small cell lung cancer (NSCLC). [0005] It has not yet been marketed in Chin...

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): C07D209/34G01N30/02
CPCC07D209/34G01N30/02G01N2030/027
Inventor 胡清文丛超王宏光于志波
Owner REYOUNG 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