Synthetic method of 2-pyridylmethyl sulfide and synthetic process of related drugs

A technology of pyridine methyl sulfide and synthesis method, applied in the direction of organic chemistry and the like, can solve problems such as environmental pollution of halogenated compounds, and achieve the effects of good applicability, high yield and high position selectivity

Active Publication Date: 2022-03-25
TIANJIN UNIV OF SCI & TECH
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this synthetic method is severely limited due to the use of highly functionalized halides as starting materials
In addition, the halides generated in the reaction have environmental pollution problems

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
  • Synthetic method of 2-pyridylmethyl sulfide and synthetic process of related drugs
  • Synthetic method of 2-pyridylmethyl sulfide and synthetic process of related drugs
  • Synthetic method of 2-pyridylmethyl sulfide and synthetic process of related drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038]

[0039] 2-Methylpyridine nitroxide (507mg, 4.65mmol) was dissolved in ethyl acetate (12ml) at room temperature, then trifluoroacetic anhydride (2.44g, 11.6mmol) was added. The reaction was refluxed for two hours. The completion of the reaction was monitored by TLC, and the reaction solution was concentrated to obtain the trifluoroacetate intermediate, which was directly used for the next step. The reaction intermediate was dissolved in toluene (6ml), then 4-methylthiophenol (577mg, 4.65mmol), tetrabutylammonium bromide (300mg, 0.93mmol) were added, and the reaction was heated under reflux for five hours, and the reaction was monitored by TLC At the end, add saturated sodium carbonate aqueous solution to the reaction solution to adjust the pH to 7-8, then separate the liquids, extract the aqueous phase with ethyl acetate three times, wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, concentrate, and use PE-PE / EA (50:1~1:3) was used as ...

Embodiment 2

[0041]

[0042] The synthetic method of embodiment 2 is the same as above-mentioned synthetic general method.

[0043] Reaction yield: 71%; Structural parameters: 1 H NMR (400MHz, CDCl 3 )δ8.54(d, J=4.4Hz, 1H), 7.62-7.58(m, 1H), 7.32(d, J=7.6Hz, 1H), 7.16-7.7.13(m, 4H), 6.98(t , J=4.0 Hz, 1H), 4.26(s, 2H), 2.28(s, 3H). 13 C NMR (100MHz, CDCl 3 )δ157.4,148.9, 138.2,136.3,135.3,129.8,128.4,126.9,126.1,122.7,121.7,40.1,21.0.HRMS (+ESI-TOF)m / z:[M+H] + Calcd for C 13 h 14 NS 216.0841; Found 216.0840.

Embodiment 3

[0045]

[0046] The synthetic method of embodiment 3 is the same as above-mentioned synthetic general method.

[0047] Reaction yield: 70%; Structural parameters: 1 H NMR (400MHz, CDCl 3 )δ8.51(d, J=4.8Hz, 1H), 7.59-7.55(m, 1H), 7.26(d, J=8.8Hz, 2H), 7.18(d, J=8.0Hz, 1H), 7.13( dd,J=5.2,6.8Hz,1H),6.77(d,J=8.8Hz,2H),4.13(s,2H),3.75(s,3H). 13 C NMR (100 MHz, CDCl3 )δ159.3, 158.1, 149.3, 136.6, 134.0, 125.6, 123.3, 122.0, 114.6, 55.3, 42.7.HRMS(+ESI-TOF)m / z:[M+H] + Calcd for C 13 h 14 NOS 232.0791; Found 232.0777.

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 a concise synthesis method of 2-picoline methyl sulfide and related medicines, specifically using 2-picoline nitrogen oxide as a raw material, ethyl acetate or dichloromethane as a solvent, and reacting with trifluoroacetic anhydride The trifluoroacetate intermediate is obtained without purification, under the catalysis of lithium bromide or tetrabutylammonium bromide, using toluene or ethyl acetate as a solvent and then reacting with thiophenol to generate 2-picolyl sulfide. The method has the obvious advantages of simple operation, cheap and easy-to-obtain reagents, mild reaction conditions, wide substrate applicability, good site selectivity and high yield. In addition, the method has been successfully applied to the synthesis of omeprazole sulfide and rabeprazole sulfide, and the synthesis process does not require any catalyst.

Description

technical field [0001] The invention belongs to the field of new compound synthesis and drug application, and relates to a synthesis method of 2-pyridylmethyl sulfide and a new synthesis process of related drugs. [0002] technical background [0003] Thioethers are ubiquitous in nature and are important synthetic precursors for many drugs or functional materials. 2-Pyridylmethylsulfide is a very important class of thioethers because it is the precursor of many biologically active compounds. In addition, it is also an important intermediate of several marketed drugs, including omeprazole, pantoprazole, lansoprazole, rabeprazole. [0004] The traditional synthesis method of thioethers uses organic halides and mercaptans as reaction raw materials, and prepares them under the action of a base, which is similar to the Williamson ether synthesis reaction. However, this synthetic method is severely limited due to the use of highly functionalized halides as starting materials. In...

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 Patents(China)
IPC IPC(8): C07D213/32C07D213/70C07D405/12C07D413/12C07D213/61C07D213/80C07D213/803C07D401/12
CPCC07D213/32C07D213/61C07D213/70C07D213/80C07D213/803C07D401/12C07D405/12C07D413/12
Inventor 王栋郁彭刘振林王振涛
Owner TIANJIN UNIV OF SCI & TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap