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

Application of solid acid catalysis multi-component reaction in preparation of fluorine-containing medicine

A multi-component reaction, solid acid catalysis technology, applied in the fields of drug combination, organic chemistry, anti-tumor drugs, etc., can solve the problems of metal catalysts that cannot be recycled, toxic solvents, etc., and achieve the effect of promoting industrialization and high-efficiency recycling ability.

Active Publication Date: 2022-05-24
ZHEJIANG SHUREN COLLEGE ZHEJIANG SHUREN UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still great challenges in the direct formation of trifluoromethyl radicals in multi-component reaction systems.
Most of the current trifluoromethylation methods use homogeneous noble metal catalysts, toxic solvents, and metal catalysts cannot be recycled

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
  • Application of solid acid catalysis multi-component reaction in preparation of fluorine-containing medicine
  • Application of solid acid catalysis multi-component reaction in preparation of fluorine-containing medicine
  • Application of solid acid catalysis multi-component reaction in preparation of fluorine-containing medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Preparation of N-methylquinoxalinone (R in structural formula (II) 1 is methyl, R 2 for H)

[0061] 2-Hydroxyquinoxalinone (12mmol, 1.75g), potassium carbonate (24mmol, 3.31g) and 15mL N,N-dimethylformamide (DMF) were added to a 100mL round-bottomed flask, and the mixture was stirred in an ice bath. Then, the DMF solution of methyl iodide (14.4 mmol, 2 g) was added dropwise to the round-bottomed flask, and the reaction was continued at room temperature for 6 hours after the dropwise addition, and the reaction was detected by TLC. After the reaction was completed, the reaction solution was washed with saturated ammonium chloride solution, extracted with ethyl acetate, the organic phase was washed with brine, the organic phase was separated, and spin-dried to obtain a crude product, which was then washed with ethyl acetate / petroleum ether (1 : 4) Carry out recrystallization to obtain purer N-methylquinoxalinone.

[0062] Preparation of N-methyl indole (R in structural ...

Embodiment 2

[0069] The effect of different catalysts

[0070] The cation exchange resins Amberlst-21 and Amberlite-732 were used to replace Amberlyst-15, respectively, and the yields of the obtained target products were 64% and 79%, respectively.

Embodiment 3

[0072] Preparation of N-propargyl quinoxalinone (R in structural formula (II) 1 is propargyl, R 2 for H)

[0073] 2-Hydroxyquinoxalinone (12mmol, 1.75g), potassium carbonate (24mmol, 3.31g) and 15mL N,N-dimethylformamide (DMF) were added to a 100mL round-bottomed flask, and the mixture was stirred in an ice bath. , and then dropwise added the DMF solution of 3-bromopropyne (14.4 mmol, 1.71 g) into the round-bottomed flask. After the dropwise addition, the reaction was continued at room temperature for 6 hours, and the reaction was detected by TLC. After the reaction was completed, the reaction solution was washed with saturated ammonium chloride solution, extracted with ethyl acetate, the organic phase was washed with brine, the organic phase was separated, and spin-dried to obtain a crude product, which was then washed with ethyl acetate / petroleum ether (1 : 4) Carry out recrystallization to obtain purer N-propargyl quinoxalinone.

[0074] Preparation of 1-propargyl-3-(1-m...

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 application of a solid acid catalyzed multi-component reaction in preparation of fluorine-containing drugs, a 3-(2-(trifluoromethyl)-indole-3-yl) quinoxaline-2-ketone derivative is efficiently synthesized by a heterogeneous solid acid catalyzed one-pot method, and compared with a fluorine-containing quinoxalinone derivative synthesized by metal homogeneous catalysis in the prior art, the method is more economical, environment-friendly and efficient. The adopted solid acid catalyst has efficient circulation capacity, and the catalytic activity can be regenerated through acidification; the 3-(2-(trifluoromethyl)-indole-3-yl) quinoxaline-2-ketone compounds with different substituent groups are efficiently expanded; the one-pot multi-component reaction system can be carried out in an environment-friendly oxidant tert-butyl hydroperoxide and a biomass solvent gamma-valerolactone, compared with industrial harsh reaction conditions under which toxic reagents are adopted, the one-pot multi-component reaction system is more environmentally friendly, and the possibility of industrialization of the reaction system is promoted.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to the application of a solid acid-catalyzed multi-component reaction in the preparation of fluorine-containing medicines. Background technique [0002] Heterocyclic compounds containing trifluoromethyl are widely found in some common drug molecules, such as the AIDS drug efavirenz, the analgesic florfenine, the non-steroidal anti-inflammatory drug indomethacin and the selective 5-HTIB / ID receptor agonist zolmitriptan, etc., its structural formula is as follows: [0003] [0004] The introduction of trifluoromethyl groups into organic heterocyclic molecules can significantly improve the physical properties, chemical properties and biological activities of organic molecules, so it is widely used in the field of medicinal chemistry. In this field, transition metal-catalyzed cross-coupling approaches have emerged as an attractive strategy to achieve this goal...

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): C07D403/04A61P35/00
CPCC07D403/04A61P35/00Y02P20/584
Inventor 童建颖沈超孙娜波章乐天郑凯吴慧珍
Owner ZHEJIANG SHUREN COLLEGE ZHEJIANG SHUREN UNIV
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