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

Macitentan related substances, and preparing methods and uses thereof

A technology of macitentan and its use, which is applied in the field of drug synthesis and can solve problems affecting product quality, etc.

Inactive Publication Date: 2019-01-01
NANJING CHIA TAI TIANQING PHARMA
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The starting materials, intermediates, by-products and degradation products in the synthesis of macitentan may become impurities remaining in the final product, thereby affecting product quality
[0005] At present, there are few literature reports on the research on related substances of macitentan and the research on quality control analysis methods

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
  • Macitentan related substances, and preparing methods and uses thereof
  • Macitentan related substances, and preparing methods and uses thereof
  • Macitentan related substances, and preparing methods and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The preparation of embodiment 1 related substance H

[0037]

[0038] Weigh 3.0g of macitentan into a single-necked bottle, add 30ml of absolute ethanol, 1.5g of Pd / C and 0.6g of ammonium formate, reflux for 4 hours, cool down to room temperature, pour the reaction solution into 300ml of citric acid aqueous solution, stir After 2h, filter with suction, and dry the filter cake to obtain 1.6g of solid. The crude product was recrystallized from methanol to obtain 1.0 g of solid. HPLC purity 100%. 1 H NMR (DMSO-d 6 ): δ9.35(1H,s),8.57(2H,d),8.50(1H,s),7.37(3H,d),7.23(3H,d),7.13(1H,t),4.66(2H, s),4.57(2H,s),2.81(2H,q),1.42(2H,m),0.80(3H,t).ESI(+)m / z 431.3

Embodiment 2

[0039] The preparation of embodiment 2 related substance H

[0040]

[0041] Weigh 3.0g of macitentan into a single-necked bottle, add 30ml of anhydrous methanol and 1.5g of Pd / C, react under hydrogen for 3h, cool down to room temperature, pour the reaction solution into 300ml of citric acid aqueous solution, and stir for 2h , filtered with suction, and the filter cake was dried to obtain 1.5 g of solid. Add 8ml of methanol, reflux for 2h, drop to room temperature, filter with suction, and dry the filter cake to obtain 0.8g of solid, HPLC purity 99.5%.

Embodiment 3

[0042] The preparation of embodiment 3 related substance J

[0043]

[0044] Add 10.0g of intermediate V, 5.1g of ammonium formate, 5.0g of Pd / C and 100ml of absolute ethanol into the reaction flask, heat to reflux for 2h, filter with suction, and rinse with 20ml of absolute ethanol. Pour the filtrate into 300ml of 10% citric acid aqueous solution, add 50ml of ethyl acetate to extract 3 times, dry the organic phase with 40.2g of anhydrous magnesium sulfate, concentrate by suction filtration to obtain a solid, add 10ml of anhydrous methanol to the solid, heat to reflux, and cool to Stir and crystallize at 20°C, filter with suction, rinse with 5 ml of anhydrous methanol, and dry the filter cake to obtain 2.1 g of Ⅴ-6.

[0045] Add 0.7g of sodium hydrogen, 21ml of tetrahydrofuran and 2.1g of Ⅴ-6 to the one-necked flask, stir for 1 hour, add 5ml of DMF and 1.4g of 5-bromo-2-chloropyrimidine, heat to 60°C, and react for 2 hours. Cool down to 25°C, pour the filtrate into 60ml of...

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

Macitentan related substances shown as a formula (I), uses thereof as macitentan impurity reference substances and a high performance liquid chromatography method for separation and measurement of macitentan and the compounds of the formula (I). Preparing methods provided are mild in reaction condition and simple in after-treatment, and can prepare the compounds of the formula (I) with purity meeting requirements in a large scale, with the compounds being adopted as impurity reference substances in macitentan quality analysis.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to macitentan-related substances, its preparation method and application. Background technique [0002] Macitentan is a dual endothelin receptor antagonist developed by Actelion. It was approved by the FDA in 2013 and is clinically used for the treatment of pulmonary arterial hypertension. Its structural formula is as follows: [0003] [0004] The quality control of raw materials and preparations has always been the focus and difficulty in drug development, and the research on impurities is the top priority in quality control. The starting materials, intermediates, by-products and degradation products during the synthesis of macitentan may become impurities remaining in the final product, thereby affecting product quality. [0005] At present, there are few literature reports on the research on related substances of macitentan and the research on quality control analy...

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): C07D239/47G01N30/02
CPCC07D239/47G01N30/02
Inventor 王留博王足兵林萍吴晶王华萍柴雨柱徐丹朱春霞田舟山
Owner NANJING CHIA TAI TIANQING 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