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

Preparation method of capmatinib

A compound and methylation technology, applied in the field of drug synthesis, can solve the problems of high energy consumption, high equipment corrosion, high environmental protection pressure, etc.

Inactive Publication Date: 2020-10-27
连庆泉
View PDF7 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] The amidation reaction in the original research process transformed compound Ⅲ into 2-fluoro-N-methyl-4-[7-[(quinolin-6-yl)methyl]imidazo[1,2-B]-[1 ,2,4] Triazin-2-yl] benzoic acid, this step reaction needs to be carried out under strong acidity and high temperature, and there are a series of problems in industrial production, such as high energy consumption, high equipment corrosion, and high environmental protection pressure.

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
  • Preparation method of capmatinib
  • Preparation method of capmatinib
  • Preparation method of capmatinib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The preparation of embodiment 1 capmatinib

[0035]

[0036] Step 1: Formula II Compound preparation

[0037] Add 38.2g (0.1mol) formula III compound to 2L reaction bottle, methylene chloride 200ml and water 100ml, 'tetrabutylammonium chloride 2g, 30% hydrogen peroxide 150ml, 20% sodium hydroxide aqueous solution 200ml, room temperature reaction 5-6 After 1 hour, add 100ml of dichloromethane after the completion of the reaction, stir and separate the liquids, wash the dichloromethane phase once with aqueous sodium sulfite solution, wash once with clear water, and concentrate the dichloromethane phase to dryness to obtain 35.1g of the title compound. The yield is 88%, and the HPLC purity is 98.5%. . MS (ESI): [M+1] = 399.5.

[0038] Step 2: Preparation of capmatinib

[0039] Add 500ml of DMF and 20.0g (0.05mol) of the compound of formula II to a 2L reaction flask, stir to dissolve, cool to 0-5°C, add 2.4g (0.06mol) of 60% sodium hydride in mineral oil in batches...

Embodiment 19

[0041] First, 2-fluoro-N-methyl-4-[7-[(quinolin-6-yl)methyl]imidazo[1,2-B]-[1,2, 4] Triazin-2-yl] benzoic acid, the specific method is as follows:

[0042]Add 2500ml of concentrated hydrochloric acid, 100ml of water, and 277.5g (0.73mol) of the compound of formula III to a 5000ml reaction flask, stir and dissolve, heat up to 100°C and reflux for 18 hours, LC-MS tracks the end of the reaction, cools the reaction solution to 80°C, and transfers to 10L stirring equipment, add 2500ml of water, cool down and crystallize, after the solid precipitates, continue to cool to 0°C, filter to obtain the solid, wash the filter cake with 1N hydrochloric acid, and dry the solid in vacuum to obtain 262.3g of the title compound, with a yield of 90%. MS (ESI): [M+1] = 400.1.

[0043] Then, prepare capmatinib with reference to Example 20 of US2009291956A1, the specific method is as follows:

[0044] In a 10L reaction vessel, add DMF3700ml, add 431.4g (0.914mol) 2-fluoro-N-methyl-4-[7-[(quinolin...

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 provides a preparation method of capmatinib. The inventor carries out wide and deep research, massive screening and testing. A compound represented by a formula III is adopted as the rawmaterial for hydrolysis reaction and methylation reaction to obtain a formula I compound, namely capmatinib. The method is mild in reaction condition, environment-friendly, low in energy consumption,good in product purity and high in yield, and is suitable for industrial large-scale production.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a preparation method of capmatinib. Background technique [0002] Capmatinib (Capmatinib, INC280) is a METex14 inhibitor developed by Novartis, Switzerland, for patients with metastatic non-small cell lung cancer (NSCLC) carrying MET exon 14 skipping mutations, including first-line treatment (naïve) patients and Previously treated (treated) patients. [0003] NSCLC accounts for approximately 85% of lung cancer diagnoses. METex14 mutations occur in 3-4% of newly diagnosed cases of advanced NSCLC, a type of lung cancer with a very poor prognosis, and there are currently no approved therapies for METex14-mutated advanced NSCLC. [0004] On February 11, 2020, the FDA accepted the New Drug Application (NDA) of the MET inhibitor capmatinib (INC280) and granted priority review, and is evaluating its application to metastatic non-small cell lung cancer carrying MET e...

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): C07D487/04
CPCC07D487/04
Inventor 连庆泉
Owner 连庆泉
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