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

A kind of benzo[b,e]azepine compound based on isatin skeleton and preparation method thereof

A compound, azapine technology, applied in the field of benzo[b,e]azepine compounds and their preparation, can solve the problem of inability to obtain seven-membered ring compounds

Active Publication Date: 2019-12-10
QINGDAO AGRI UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, tetrahydropyrrolidine is a common substrate for the synthesis of nitrogen heterocyclic compounds. However, the ring-shaped products obtained by using the ring-opening and ring-expanding reaction of tetrahydropyrrolidine are all six-membered rings, eight-membered rings and nine-membered rings. ring, and the seven-membered ring compound cannot be obtained

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 kind of benzo[b,e]azepine compound based on isatin skeleton and preparation method thereof
  • A kind of benzo[b,e]azepine compound based on isatin skeleton and preparation method thereof
  • A kind of benzo[b,e]azepine compound based on isatin skeleton and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048]

[0049] Take 0.1 mmol of 1-benzyl-4-pyrrolidinyl isatin in a reaction bottle, add 2 mL of solvent in sequence, vertically drop 0.3 mmol of p-cresol into the bottle, and finally add the catalyst. Control the temperature of the system, keep stirring, and track the reaction by pointing samples on the thin-layer chromatographic plate until the reaction of the raw materials is complete.

[0050] After the reaction is completed, a silica gel column is used for separation and purification, and the purified product is rotary evaporated to obtain the target product.

[0051] Using the above reaction formula, 19 parallel test groups were set up, using different catalysts, solvents and reaction times. The catalysts are MsOH methanesulfonate, TfOH trifluoromethanesulfonate, Tf trifluoromethanesulfonamide 2 NH, samarium trifluoromethanesulfonate Sm (OTf) 3 , scandium trifluoromethanesulfonate Sc(OTf) 3 , Iridium trifluoromethanesulfonate Y (OTf) 3 , Gadolinium trifluorometha...

Embodiment 2

[0059] Raw materials: 1-benzyl-4-pyrrolidinyl isatin, p-cresol

[0060] Product: Chemical formula: C 26 h 25 N 2 o 3

[0061] Molecular weight: 412.49

[0062] Structural formula:

[0063] Yield: 59%

[0064] 1 H NMR (500MHz, CDCl 3 )δ7.52(s,1H),7.40–7.16(m,5H),6.97–6.85(m,2H),6.72(d,J=8.0Hz,1H),6.54(d,J=7.7Hz,1H ), 5.76(d, J=7.7Hz, 1H), 5.28(s, 1H), 4.77(q, J=15.6Hz, 2H), 4.58(dd, J=10.5, 2.3Hz, 1H), 3.74(ddd ,J=12.8,7.8,3.5Hz,1H),3.46–3.31(m,1H),2.45(ddd,J=16.4,12.2,5.9Hz,1H),2.25(s,3H),2.13–2.04(m ,1H),2.04–1.90(m,2H); 13 C NMR (125MHz, CDCl 3 )δ181.43,160.84,152.20,150.95,147.20,139.31,135.57,130.15,130.07,129.48,128.80,128.29,127.83,127.53,127.39,115.91,103.65,98.72,44.11,43.88,40.30,31.02,27.17,20.71.

Embodiment 3

[0066] Raw materials: 1-(4-methylbenzyl)-4-pyrrolidinyl isatin, p-cresol

[0067] Product: Chemical formula: C 27 h 26 N 2 o 3

[0068] Molecular weight: 426.52

[0069] Structural formula:

[0070] Yield: 45%

[0071] 1 H NMR (500MHz, CDCl 3 )δ7.51(s,1H),7.15(d,J=7.5Hz,2H),7.09(d,J=7.5Hz,2H),6.93(d,J=7.9Hz,1H),6.89(s, 1H), 6.70(d, J=8.0Hz, 1H), 6.54(d, J=7.6Hz, 1H), 5.78(d, J=7.6Hz, 1H), 5.05(s, 1H), 4.81–4.66( m,2H),4.57(d,J=10.2Hz,1H),3.81–3.66(m,1H),3.47–3.33(m,1H),2.44(dd,J=19.5,8.7Hz,1H),2.29 (s,3H),2.25(s,3H),2.13–2.04(m,1H),1.97(s,2H); 13 C NMR (125MHz, CDCl 3 )δ181.59,160.80,152.16,150.90,147.30,139.30,137.60,132.54,130.19,130.13,129.48,128.30,127.57,127.24,115.86,103.65,98.79,44.12,43.64,40.31,30.98,27.15,21.12,20.74.

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 present invention provides a benzo[b,e]azepine compound based on an isatin skeleton, and the unique skeleton structure of the benzo[b,e]azepine compound has good antibacterial activity. A preparation method of benzo[b,e]azepine by a Lewis acid-catalyzed pyrrolidine ring-expansion synthesis process is also developed. The synthesis of polycyclic amines with complex structures is carried out by one-step method by use of 4-pyrrolidine isatin and various phenol compounds as substrates, and synthesis strategies of the polycyclic amines from pyrrolidine are extended. The synthetic method of the benzo[b,e]azepine compound has the advantages of convenient and easy-to-obtain substrate, convenient operation, high reaction activity, complete conversion of raw materials, and green economy.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and relates to a benzo[b,e]azepine compound based on an isatin skeleton and a preparation method thereof. Background technique [0002] The seven-membered nitrogen heterocyclic ring is a special class of compounds, mainly composed of heterocyclic compounds; the special structure of the seven-membered ring has significant physiological and pharmacological effects, and the potential pharmacological properties of these compounds are mainly explored in the Anticancer and antibacterial aspects. For example, Tolvaptan, a competitive antidiuretic hormone receptor blocker, and Mirtazapine, one of the eight major antidepressants. [0003] At present, the reaction strategies for the synthesis of seven-membered azacyclic 1-benzazepines include Pictet-Spengler reaction, NHC / Pd catalyzed cyclization, Ichikawa rearrangement and ring closure reaction, etc. In 1895, the "tertiary amine effect" was ...

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): C07D487/04A01P1/00A01P3/00A61P31/04A61P31/10
CPCA61P31/04A61P31/10C07D487/04
Inventor 肖建王帅李帅帅于丽萍
Owner QINGDAO AGRI 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