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

Fluoroalkyl sulfonyl fluoride compound as well as intermediate, preparation method and application thereof

A compound and fluoroalkyl technology, which is applied in the preparation of sulfonic acid, organic chemistry, drug combination, etc., can solve the problems of small fluoroalkyl substrates, high toxicity, and volatility of reagents, etc.

Active Publication Date: 2019-01-04
SHANGHAI INST OF ORGANIC CHEMISTRY - CHINESE ACAD OF SCI
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The technical problem to be solved by the present invention is to overcome the narrow scope of application of substrates in the preparation method of compounds containing fluoroalkylsulfonyl fluoride in the prior art, the type of fluoroalkyl group is limited to trifluoromethyl, poor functional group compatibility, harsh reaction conditions, Due to the disadvantages of reagents such as volatility and high toxicity, a fluoroalkylsulfonyl fluoride compound and its intermediate, preparation method and application are provided

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
  • Fluoroalkyl sulfonyl fluoride compound as well as intermediate, preparation method and application thereof
  • Fluoroalkyl sulfonyl fluoride compound as well as intermediate, preparation method and application thereof
  • Fluoroalkyl sulfonyl fluoride compound as well as intermediate, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0120]

[0121] Zinc powder (0.3mmol) and sodium dithionite (0.6mmol) were added to the reaction flask, the argon was replaced three times, and DMF (4.5mL), H 2 O (75 uL), 4-phenyl-1-butene (0.3 mmol) and ethyl difluorobromoacetate (0.6 mmol). The reaction flask was placed at 25°C and stirred for 10 hours. NFSI (1.2 mmol) was added under the protection of argon, and stirred at room temperature for 3 h. With 4-(trifluoromethoxy)anisole as internal standard substance, using 19 F-NMR confirmed the formation of the target product. The reaction solution was filtered, and the filtrate was used to remove the solvent by a rotary evaporator, separated by column chromatography, and concentrated under reduced pressure to obtain a light yellow liquid (51% yield). The relevant data are as follows: 1 H NMR (400MHz, CDCl 3 ):δ7.33(t, J=7.3Hz, 2H), 7.28–7.24(m, 1H), 7.23–7.19(m, 2H), 4.36(q, J=7.1Hz, 2H), 3.81–3.73( m,1H),3.01–2.83(m,3H),2.65–2.51(m,1H),2.49–2.37(m,1H),2.34–2.25(m,1H...

Embodiment 2

[0123]

[0124] Zinc powder (0.6mmol) and DABSO (0.6mmol) were added to the reaction flask, the argon gas was replaced three times, and DMF (4.5mL), H 2 O (75 uL), 4-phenyl-1-butene (0.3 mmol) and ethyl difluorobromoacetate (0.6 mmol). The reaction flask was placed at -5°C and stirred for 6 hours. NFSI (1.2 mmol) was added under the protection of argon, and stirred at room temperature for 3 h. With 4-(trifluoromethoxy)anisole as internal standard substance, using 19 F-NMR confirmed the formation of the target product. Filter the reaction solution, wash the solid impurities with dichloromethane, wash three times with water, wash once with saturated brine, dry the organic phase with anhydrous sodium sulfate, remove the solvent by rotary evaporator after filtration, separate by column chromatography, and concentrate under reduced pressure to obtain light yellow Liquid (69% yield). Relevant data see embodiment 1.

Embodiment 3

[0126]

[0127] Zinc powder (0.6mmol) and DABSO (0.6mmol) were added to the reaction flask, the argon gas was replaced three times, and DMF (4.5mL), H 2 O (75 uL), 4-phenyl-1-butene (0.3 mmol) and N,N-diethyldifluorobromoacetamide (0.6 mmol). The reaction flask was placed at -5°C and stirred for 12 hours. NFSI (1.2 mmol) was added under the protection of argon, and stirred at room temperature for 3 h. With 4-(trifluoromethoxy)anisole as internal standard substance, using 19 F-NMR confirmed the formation of the target product. Filter the reaction solution, wash the solid impurities with dichloromethane, wash three times with water, wash once with saturated brine, dry the organic phase with anhydrous sodium sulfate, remove the solvent by rotary evaporator after filtration, separate by column chromatography, and concentrate under reduced pressure to obtain light yellow Liquid (66% yield). The relevant data are as follows: 1 H NMR (400MHz, CDCl 3):δ7.31(t,J=7.3Hz,2H),7.26...

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 discloses a fluoroalkyl sulfonyl fluoride compound as well as an intermediate, a preparation method and the application thereof. The preparation method of the fluoroalkyl sulfonyl fluoride compound shown as a formula I has the advantages of wide application range of substrates, no limitation to trifluoromethyl in fluoroalkyl types, good compatibility of functional groups, mild reaction conditions and the like. The fluoroalkyl sulfonyl fluoride compound disclosed by the invention has better JAK kinase inhibitory activity and further has a better application and popularization prospect.

Description

technical field [0001] The invention relates to a fluoroalkylsulfonyl fluoride compound and its intermediate, preparation method and application. Background technique [0002] The fluorine atom has the characteristics of small atomic radius, low polarizability, high electronegativity and strong C-F bond. When fluorine atoms are introduced into the drug molecule, the fat solubility of the molecule can be increased, thereby enhancing the membrane penetration of the fluorine-containing compound in the organism and promoting the absorption and utilization of the drug; since the fluorine atom has a volume similar to that of the hydrogen atom , so that the volume of the entire molecule does not change much after replacing the hydrogen atoms in the molecule with fluorine atoms, so fluorine-containing drugs are usually not recognized by biological enzymes, showing a "pseudo-pseudo effect". The C-F bond has a very high bond energy. After the fluorine-containing compound enters the o...

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): C07C303/02C07C309/84C07C309/85C07C309/82C07C309/81C07D209/48C07C313/04A61P35/00A61P31/00A61P29/00A61P37/06
CPCA61P29/00A61P31/00A61P35/00A61P37/06C07C303/02C07C309/81C07C309/82C07C309/84C07C309/85C07C313/04C07D209/48C07C2601/18
Inventor 刘超陈庆云刘永安林琼珍肖智伟
Owner SHANGHAI INST OF ORGANIC CHEMISTRY - CHINESE ACAD OF SCI
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