Unlock instant, AI-driven research and patent intelligence for your innovation.

Afatinib degradation impurity compound as well as preparation method and application thereof

A technology of afatinib and compounds, applied in the field of afatinib to degrade impurity compounds, can solve the problem of affecting the quality of afatinib maleate raw materials and related preparations, and unfavorable quality control of afatinib net drug production process optimization and other issues, to achieve the effect of improving quality control standards, simple and efficient preparation method, and novel structure

Inactive Publication Date: 2019-12-13
BEIJING ZHENDONG GUANGMING PHARMA RES INST
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] During the preparation and storage of afatinib, due to alkaline environment, humid environment and other factors, degraded impurities will be generated. Although the structures of some afatinib impurities have been analyzed, there are still other impurities with unknown structures , will affect the quality of afatinib maleate API and related preparations, which is not conducive to the quality control of afatinib net drug and the optimization of the production process

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
  • Afatinib degradation impurity compound as well as preparation method and application thereof
  • Afatinib degradation impurity compound as well as preparation method and application thereof
  • Afatinib degradation impurity compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0044] As an embodiment, the method for the impurity compound includes:

[0045] In the presence of an organic solvent, the afatinib is reacted with a basic substance to obtain the afatinib-degraded impurity compound.

[0046] As an embodiment, the alkaline substance includes at least one of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide and potassium hydroxide.

[0047] As an embodiment, the alkaline substance is at least one selected from sodium hydroxide or potassium hydroxide.

[0048] As an embodiment, the molar ratio of the afatinib to the basic substance is 1:1-1:30. Optionally, the lower limit of the molar ratio of the afatinib to the basic substance is independently selected from 1:1, 1:2, 1:3, 1:5, 1:8, 1:10, 1:1 15, 1:20, 1:25, 1:28, 1:30; the upper limit of the molar ratio of the afatinib to the basic substance is independently selected from 1:1, 1:5, 1:8, 1:10, 1:15, 1:20, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30. ...

Embodiment 1

[0053] Embodiment 1 Preparation of afatinib degradation impurity compound

[0054] 1 # compound

[0055]Add 680mL of absolute ethanol, 170mL of water and 17.40g of potassium hydroxide to a 1.0L single-necked bottle in sequence, stir and dissolve, then add 15.00g of afatinib, and stir at 50°C for 24h.

[0056] Concentrate under reduced pressure to remove ethanol, adjust the pH of the reaction solution to 7-8 with 3M hydrochloric acid solution, a white solid precipitates out, filter, retain the white solid, and dry it at 50°C to obtain the afatinib degradation impurity compound (I) 13.22g, yield 93.3%, purity 99.50%. record as 1 # compound. The reaction scheme is shown in the following formula:

[0057]

[0058] 2 # compound

[0059] Add 120mL of isopropanol, 30mL of water and 4.0g of sodium hydroxide into a 500mL single-necked bottle, stir well, add 5.66g of afatinib, and stir at 70°C for 18h.

[0060] Concentrate under reduced pressure to remove isopropanol, adj...

experiment example 1

[0070] Experimental Example 1 Compound Structural Characterization

[0071] The structure of the afatinib impurity compound prepared in Example 1 was confirmed by mass spectrometry and nuclear magnetic resonance.

[0072] Mass spectrometry characterization results: Mass spectrometry characterization results such as figure 1 As shown, the molecular ion peak chemical formula is C 22 h 21 N 4 o 4 For FCl(+), the exact mass number of the molecular ion peak is 459.1232, which is consistent with the structure of the compound represented by formula (I).

[0073] NMR characterization results:

[0074] 1 H-NMR (400MHz, DMSO-d6) δppm: 9.88 (s, 1H), 8.528 (s, 1H), 8.38 (s, 1H), 8.18 (dd, J1 = 6.5Hz, J2 = 2.5Hz, 1H), 7.82-7.84 (m, 1H), 7.42 (t, J=9Hz, 1H), 7.29, 7.30 (split, 1H), 6.33 (brs, 1H), 5.45-5.52 (m, 1H), 5.25-5.31 ( m,1H), 3.94-3.99(m,1H), 3.75-3.88(m,3H), 2.54-2.62(m,1H), 2.36-2.47(m,2H), 2.3123-2.32(m,1H), 1.98-2.06 (m, 1H), 1.88-1.92 (m, 1H).

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 relates to an afatinib degradation impurity compound as well as a preparation method and application thereof. The structural formula of the impurity compound is shown as a formula(I). The preparation method of the impurity compound is simple and efficient, and the impurity compound can be used as a quality control standard substance or a reference substance of afatinib bulk drugs orpreparations.

Description

technical field [0001] The invention relates to the fields of medicine and chemical synthesis, in particular to afatinib degradation of impurity compounds, its preparation method and application. Background technique [0002] Afatinib is a lung cancer drug developed by Boehringer Ingelheim in Germany. The drug was approved for marketing in the United States in July 2013. As a multi-target small molecule drug, it is a potent and irreversible dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal receptor 2 (HER2) tyrosine kinase. As a new first-line treatment drug, it is clinically used in the treatment of advanced non-small cell lung cancer, advanced breast cancer, and colon cancer; at the same time, afatinib has been selected for research purposes in various tumor types, and is currently undergoing phase III trials for head and neck cancer. Clinical Trials. [0003] Afatinib (Afatimib), the chemical name is 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-...

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): C07D405/14G01N24/08G01N30/02G01N30/72
CPCC07D405/14G01N24/087G01N30/02G01N30/72
Inventor 张居稳雷飞张永林
Owner BEIJING ZHENDONG GUANGMING PHARMA RES INST
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com