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

4-(substituted-1,3-dialkynyl)-4-(trifluoromethyl)benzo-1,4-dihydroxazole-2-one compounds and preparation method and applications thereof

A technology of ketone compound and trifluoromethyl, which is applied in the field of benzo-1, achieves the effects of high yield, simple and feasible synthesis method, and good application value

Inactive Publication Date: 2011-07-20
TIANJIN UNIV
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

4-Diynyl-4-trifluoromethylbenzo-1,4-dihydrooxazin-2-one compounds, preparation methods and anti-HIV, HBV and HCV have not been reported in the existing literature

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
  • 4-(substituted-1,3-dialkynyl)-4-(trifluoromethyl)benzo-1,4-dihydroxazole-2-one compounds and preparation method and applications thereof
  • 4-(substituted-1,3-dialkynyl)-4-(trifluoromethyl)benzo-1,4-dihydroxazole-2-one compounds and preparation method and applications thereof
  • 4-(substituted-1,3-dialkynyl)-4-(trifluoromethyl)benzo-1,4-dihydroxazole-2-one compounds and preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0028] Example 1: When R is a cyclopropyl group, R 1 When it is 5-chloro, the synthesis of intermediate A:

[0029]

[0030] In a dry and argon-substituted 100 mL Schlenck reaction flask, add (1R,2S)-1-phenyl-2-(1-pyrrole) n-propan-1-ol (4.52 g, 22 mmol) and triphenylmethane (0.1 g), dissolved in anhydrous THF (10 mL). The mixture was cooled to -10°C, and 18.4mL (44mmol) of n-butyllithium in n-hexane (2.4M in hexanes) was slowly added to ensure that the temperature was below 5°C, and the addition was completed in 2 hours to obtain a wine-red solution. 4-Cyclopropyl-1,3-butadiyne (1.98 g, 22 mmol) was added and the addition was completed in 30 minutes. Stirring was continued at 0-5°C for 30 minutes, then cooled to -60°C. Add 5-chloro-2-(4'-methoxybenzylamino)phenyltrifluoromethylketone (3.44g, 10mmol) in tetrahydrofuran (5mL) dropwise into the wine red mixture to ensure the internal temperature of the reaction Below -50~-55°C. The reaction was continued to stir at this ...

example 2

[0031] Example 2: (S)-6-Chloro-4-(4-cyclopropanylbut-1,3-diynyl)-4-(trifluoromethyl)benzo-1,4-dihydrooxazine- 2-keto (S-1)

[0032]

[0033] 4.01 grams (9.2 mmol) of the compound obtained in Experiment 1 and triethylamine (2.32 g, 23 mmol) were dissolved in 12 mL of toluene, and then 20% phosgene toluene solution (11 g, 11.0 mmol) was added at room temperature for 30 minutes After the addition was complete, stirring was continued at this temperature for 1 hour. Methanol (0.12 g, 3.6 mmol) was added to react with unreacted phosgene for 30 minutes, 10 mL of water and 10 mL of ethyl acetate were added, the reaction mixture was transferred to a separatory funnel, and the organic layer was obtained by liquid separation. After drying, the solvent was removed under reduced pressure, separated by column chromatography, and a colorless viscous compound was obtained quantitatively.

[0034]The obtained viscous compound was dissolved in 20 mL of acetonitrile, 20 mL of an aqueous sol...

example 3

[0035] Example 3: (R)-6-chloro-4-(4-cyclopropanylbut-1,3-diynyl)-4-(trifluoromethyl)benzo-1,4-dihydrooxazine- 2-keto (R-1)

[0036]

[0037] A method similar to Example 1 and 2 uses 0.05 equivalents of (1S, 2S)-2-benzylmethylamino-1-(4-nitrophenyl)-3-(trityloxy) n-propan-1-alcohol As a chiral ligand, (R)-6-chloro-4-(4-cyclopropanylbut-1,3-diynyl)-4-(trifluoromethyl)benzo-1,4- Dihydrooxazin-2-one (R-1), yield 53%, 85% ee.

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 4-(substituted-1,3-dialkynyl)-4-(trifluoromethyl)benzo-1,4-dihydroxazole-2-one compounds and a preparation method and applications thereof. The preparation method is as follows: substituted-2-(2-(4-methoxybenzylamino)phenyl)-1,1,1-trifluoro-3,5-hexyne-2-ol reacts with phosgene in organic solvent at the temperature ranging from -20 DEG C to 30 DEG C under the action of alkali; after the reaction, the pressure is reduced to remove solvent, and then the obtained product reacts with ammonium ceric nitrate in organic solvent to obtain the target compounds. In the method, bialkynyl group is introduced in 4-trifluoromethylbenzo-1,4-dihydroxazole-2-one, the synthesis method is simple and practical and has high yield; and the compounds are used to prepare anti-HIV drugs oranti-HBV drugs or anti-HCV drugs and have better application value. The anti-HIV drugs are anti-AIDS drugs; the anti-HBV drugs are anti-hepatitis B drugs; and the anti-HCV drugs are anti-hepatitis C drugs. The structural general formula of the compounds of the invention is shown as below.

Description

technical field [0001] The present invention relates to a class of benzo-1,4-dihydrooxazin-2-ketone compounds, preparation method and application thereof, especially 4-diynyl-4-trifluoromethylbenzo-1,4 -Dihydrooxazin-2-one compounds, preparation methods and applications thereof. Background technique [0002] Virus infection causes various diseases, which seriously endanger human health and life. About 60% of epidemic infectious diseases are caused by virus infection. So far, more than 3,000 kinds of viruses have been discovered in the world, such as: influenza virus, hepatitis virus (such as HBV, HCV, etc.), and AIDS virus (HIV). Antiviral drugs are only virus inhibitors (Virustatic agents), which inhibit the reproduction of viruses, repair damaged tissues, and alleviate the disease so that no clinical symptoms appear. For example, currently developed chemotherapeutic AIDS drugs are all reverse transcriptase inhibitors, which can prevent the extension of mDNA and interfere...

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): C07D265/18C07D413/06C07D407/06C07C213/00C07C217/58C07C217/84C07D213/38C07D307/52A61K31/536A61P31/14A61P31/16A61P31/18A61P1/16
Inventor 马军安马海郑艳
Owner TIANJIN 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