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

A class of 2-substituted tetrahydroquinoline compounds and their derivatives, preparation methods and applications

A tetrahydroquinoline, compound technology, applied in the directions of organic chemistry, drug combination, antitumor drugs, etc., can solve problems such as damage to sustainability, and achieve the effect of green preparation method

Active Publication Date: 2022-01-14
DALIAN UNIV OF TECH
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the methods mentioned above often require homogeneous catalysts based on rare, expensive, or even toxic noble metals, thus compromising sustainability (S.A.Girard, T.Knauber, C.Li, Angew.Chem.Int.Ed, 2014, 53, 74-100)

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
  • A class of 2-substituted tetrahydroquinoline compounds and their derivatives, preparation methods and applications
  • A class of 2-substituted tetrahydroquinoline compounds and their derivatives, preparation methods and applications
  • A class of 2-substituted tetrahydroquinoline compounds and their derivatives, preparation methods and applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Preparation of compound I-1 (N-benzyl-2-nitromethyl-1,2,3,4-tetrahydroquinoline)

[0081] R 1 is benzyl; R 2 is hydrogen; R 3 for hydrogen

[0082] Take compound 1-1 (0.25mmol) in a 15ml thick-walled pressure bottle, weigh the metal catalyst ZnBr 2 (0.025mmol, 5.7mg) was added to a thick-walled pressure bottle, and nitromethane (500 μl) was added to the pressure bottle, N 2 Protection, stirring reaction at 100 ° C for 24h. After the reaction, the reaction solution was transferred to a 25ml eggplant-shaped bottle using dichloromethane, concentrated under reduced pressure, and the crude product was subjected to silica gel column chromatography, and the eluent was petroleum ether:ethyl acetate=30:1 (v / v) , separation and purification to obtain pure product, light yellow solid, yield: 65% (45.8mg); 1 H-NMR (400MHz, CDCl 3 ): δ7.30(t, J=7.3Hz, 2H), 7.23(dd, J=14.1, 7.1Hz, 3H), 7.04(d, J=7.4Hz, 1H), 6.99(t, J=7.8Hz ,1H),6.67(t,J=7.3Hz,1H), 6.55(d,J=8.3Hz,1H),4.62(ABq,...

Embodiment 2

[0084] Preparation of compound I-2 (N-phenyl-2-nitromethyl-1,2,3,4-tetrahydroquinoline)

[0085] R 1 is phenyl; R 2 is hydrogen; R 3 for hydrogen

[0086] Get compound 1-2 (0.25mmol) in 15ml thick-walled pressure bottle, weigh metal catalyst ZnBr 2 (0.025mmol, 5.7 mg) into a thick-walled pressure bottle, measure nitromethane (500μl) into the pressure bottle, N 2 Protection, stirring reaction at 100 ° C for 24h. After the reaction, the reaction solution was transferred to a 25ml eggplant-shaped bottle using dichloromethane, concentrated under reduced pressure, and the crude product was subjected to silica gel column chromatography, and the eluent was petroleum ether:ethyl acetate=30:1 (v / v) , separation and purification to obtain pure product, yellow oily liquid; yield: 61% (40.8mg); 1 H-NMR (400MHz, CDCl 3 ): δ7.36(t, J=7.8Hz, 2H), 7.20-7.14(m, 3H), 7.09(d, J=7.5Hz, 1H), 6.96(t, J=7.7Hz, 1H), 6.79 (t, J=7.4Hz, 1H), 6.62(d, J=8.2Hz, 1H), 4.63-4.44(m, 3H), 2.93-2.84(m, 2...

Embodiment 3

[0088] Preparation of compound I-3 (N-allyl-2-nitromethyl-1,2,3,4-tetrahydroquinoline)

[0089] R 1 is allyl; R 2 is hydrogen; R 3 for hydrogen

[0090] Take compound 1-3 (0.25mmol) in a 15ml thick-walled pressure bottle, weigh the metal catalyst ZnBr 2 (0.025mmol, 5.7 mg) into a thick-walled pressure bottle, measure nitromethane (500μl) into the pressure bottle, N 2 Protection, stirring reaction at 100 ° C for 24h. After the reaction, the reaction solution was transferred to a 25ml eggplant-shaped bottle using dichloromethane, concentrated under reduced pressure, and the crude product was subjected to silica gel column chromatography, and the eluent was petroleum ether:ethyl acetate=30:1 (v / v) , separation and purification to obtain pure product, yellow oily liquid, yield: 55% (31.9mg); 1 H-NMR (400MHz, CDCl 3 ): δ7.08(t, J=7.8Hz, 1H), 7.03(d, J=7.3Hz, 1H), 6.69(t, J=7.3Hz, 1H), 6.63(d, J=8.3Hz, 1H ),5.85(ddt,J=15.6,10.0,4.9Hz,1H), 5.24-5.16(m,2H),4.53(dd,J=11.5,5.6Hz...

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 belongs to the technical field of medicine and chemical industry, and relates to a class of 2-substituted tetrahydroquinoline compounds and their derivatives, preparation methods and applications. The 2-substituted tetrahydroquinoline compound and its derivatives prepared by the present invention have antimalarial activity, can be used as a variety of pharmaceutical key intermediates, and can be applied to the preparation of antitumor drugs and HIF-1 inhibitors. The preparation method is green , simplified and efficient.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and more specifically relates to a class of 2-substituted tetrahydroquinoline compounds and their derivatives, preparation methods and applications. Background technique [0002] Hypoxia-inducible factor HIF-1 is a basic helix-loop-helix (bHLH-PAS) family protein that forms a heterodimer from its α and β subunits and functions as a transcription factor. HIF-1βis expressed in any state, and HIF-1αis regulated by oxygen status. Under oxygen-enriched conditions, the production and degradation of HIF-1α are in balance. During this process, two proline sites (Pro402 and Pro564) in the oxygen-dependent degradation (ODD) domain are hydroxylated by prolyl hydroxylase. Of the three prolyl hydroxylases (PHD1, PHD2 and PHD3) in mammalian cells, PHD2 is known to play a major role. Under normoxia, PHD2 uses molecular oxygen and 2-oxoglutarate (α-ketoglutarate) as co-substrates for th...

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): C07D215/12C07D471/04C07D215/20C07D215/06C07D215/14C07D215/18C07D405/06C07D401/04A61P35/00
CPCC07D215/12C07D471/04C07D215/20C07D215/06C07D215/14C07D215/18C07D405/06C07D401/04A61P35/00
Inventor 李广哲王成栋邵堃李悦青王世盛赵伟杰郭修晗
Owner DALIAN UNIV OF TECH
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