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

Method for synthesizing 3-quinoline derivatives

A technology of derivatives and fluoroquinoline, applied in the field of synthesizing 3-fluoroquinoline derivatives, can solve the problem of large amount of catalyst, and achieve the effects of convenient separation, mild reaction conditions, and easy availability of raw materials

Active Publication Date: 2015-06-03
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this type of reaction still cannot get rid of the shortcomings of large amount of catalyst or the need to introduce positioning groups.

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
  • Method for synthesizing 3-quinoline derivatives
  • Method for synthesizing 3-quinoline derivatives
  • Method for synthesizing 3-quinoline derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1: the synthesis of compound 2a

[0027] In a nitrogen-protected reaction flask, add 1a (0.2 mmol), p-toluenesulfonic acid monohydrate (0.01 mmol), HEH (0.22 mmol), and then add 3 ml of dry acetonitrile. After reacting at room temperature for 2 hours, Add Selectfluor (0.3 mmol) and continue the reaction for 5 minutes, then add potassium tert-butoxide (0.4 mmol) to the system, continue stirring at room temperature for 2 hours, remove the solvent under reduced pressure, and obtain the compound by silica gel column chromatography 2a, its isolated yield reached 94%. The reaction formula is as follows:

[0028]

[0029] 3-Fluoro-2-phenylquinoline(2a):94%yield,white solid,m.p.=36-38℃,R f =0.50(petroleum ether / EtOAc=20:1); 1 H NMR (400MHz, CDCl 3 )δ8.16(d,J=8.5Hz,1H),8.07(d,J=7.3Hz,2H),7.87-7.61(m,3H),7.56-7.44(m,4H); 13 C NMR (100MHz, CDCl 3 )δ155.2(d, 1 J F C=261.0Hz),149.2(d, 2 J FC =14.5Hz), 145.4(d, 5 J FC =2.9Hz), 135.9(d, 4 J FC =5.2Hz), 129....

Embodiment 2

[0031] The synthesis process of compounds 2b-2p is the same as that of Example 1, the difference from Example 1 is that only the substituents R and R' on the raw material 1a are different.

[0032] 3-Fluoro-2-o-tolylquinoline (2b): 95% yield, white solid, m.p.=69-71℃, R f =0.40(petroleum ether / EtOAc=20:1); 1 H NMR (400MHz, CDCl 3 )δ8.17(d,J=8.4Hz,1H),7.87-7.54(m,4H),7.46-7.30(m,4H),2.30(s,3H); 13 C NMR (100MHz, CDCl 3 )δ154.8(d, 1 J FC =257.8Hz), 151.7(d, 2 J FC =19.2Hz), 145.3(d, 4 J FC =2.9Hz),137.0,135.7(d, 4 J FC =3.6Hz),130.7,130.0(d, 5 J FC =1.6Hz),129.8,129.4,128.95(d, 5 J FC =2.5Hz), 128.66(d, 3 J FC =5.1Hz), 127.6, 127.15(d, 3 J FC =4.9Hz), 126.1, 119.2(d, 2 J FC =18.9Hz), 19.9(d, 4 J FC =2.9Hz); 19 F NMR (376MHz, CDCl 3 )δ-123.4(d,J=5.4Hz);HRMS(ESI)m / z Calculated for C 16 h 12 FN[M+H] + 238.1027, found 238.1034.

[0033] 3-Fluoro-2-m-tolylquinoline (2c):93%yield,colorless oil,R f =0.50(petroleum ether / EtOAc=20:1); 1 H NMR (400MHz, CDCl ...

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 method for synthesizing 3-quinoline derivatives. The method comprises the following steps: based on a simple 3-nitroquinoline, with bronsted acid as a catalyst, substituting 1,4-dihydropyridine (HEH) as a reducing agent, realizing 1,4- reduction of quinoline to obtain enamine, performing electrophilic addition on the enamine intermediate and a fluorinated reagent, and then repeatedly aromatizing under an alkali condition to obtain various substituted 3-quinoline derivatives. The method for synthesizing the 3-quinoline derivatives has the advantages that the operation is simple, convenient and practical, the raw materials are easy to obtain, the reaction is quick, the post-treatment is convenient, and the yield is high.

Description

technical field [0001] The invention relates to aromatic heterocyclic compounds containing fluorine atoms, in particular to a method for synthesizing 3-fluoroquinoline derivatives. Background technique [0002] Fluorine-containing organic compounds are widely used in the fields of medicine, pesticides, and materials due to their stable carbon-fluorine bonds, fluorocarbon phase characteristics, lipophilicity, pseudo-mimetic effect, metabolic stability, and hydrogen bonding. Especially in medicine, a class of drugs with fluorine-containing aromatic compounds as active groups plays a pivotal role. According to reports, among all commercialized medicines and pesticides, the proportion of fluorine-containing drugs is as high as about 20%. [Document 1: a) H.Schofield, J.Fluorine Chem.1999,100,7; b) H.J.Bohm, D.Banner, S.Bendels, M.Kansy, B Kuhn, K.Muller, U.Obst-Sander , M.Stahl, ChemBioChem2004, 5, 637; c) K.Muller, C.Faeh, F.Diederich, Science2007, 317, 1881; d) W.K.Hagmann, J...

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): C07D215/18C07D215/20
CPCC07D215/18C07D215/20
Inventor 周永贵郭冉柠时磊
Owner DALIAN INST OF CHEM PHYSICS 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