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

Chiral benzodiazepine compound and synthesis method thereof

A synthesis method and benzodiazepine technology are applied in the field of chiral benzodiazepine compounds and their synthesis, and achieve the effects of good application prospect, reduced production cost and simple process operation

Inactive Publication Date: 2017-10-27
JILIN UNIV +1
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Catalytic synthesis of chiral benzodiazepines Compounds are rarely reported

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
  • Chiral benzodiazepine compound and synthesis method thereof
  • Chiral benzodiazepine compound and synthesis method thereof
  • Chiral benzodiazepine compound and synthesis method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1: Preparation of chiral benzodiazepines

[0034] Dissolve 2-(1H-indoline)aniline (21g, 0.1mol) and pyruvate-2-naphthyl ester (21g, 0.1mol) in 1L tetrahydrofuran, and add 1-naphthyl at the 3,3' position while stirring The H8-BINOL derived phosphoramidite acid (0.2g) and Molecular sieves (70g) were reacted at 30°C for 48 hours. After the reaction was complete, the product was purified by column chromatography to obtain a white solid (36.5g, 93%, 95%ee). 95%ee[Daicel Chiralcel AD-H column, n-hexane / i-PrOH=70:30, 1.0mL / min, λ=254nm, t(minor)=37.20min, t(major)=21.58min]; 1 H NMR (300MHz, DMSO-d 6 )δ7.90–7.71(m,3H),7.54–7.43(m,2H),7.19–6.99(m,5H),6.94–6.79(m,2H),6.73–6.58(m,2H),5.92( s, 1H), 4.12–3.96 (m, 1H), 3.84 (dd, J=16.3, 7.1 Hz, 1H), 3.19–3.02 (m, 2H), 2.00 (s, 3H).

Embodiment 2

[0035] Embodiment 2: Preparation of chiral benzodiazepines

[0036] Dissolve 2-(1H-indoline)aniline (6.3g, 30mmol) and pyruvate-2-naphthyl ester (6.3g, 30mmol) in 200mL ether, and add 1-naphthyl at the 3,3' position while stirring The H8-BINOL derived phosphoramidite acid (0.2g) and Molecular sieves (80g) were reacted at 30°C for 48 hours. After the reaction was complete, the product was purified by column chromatography to obtain a white solid (10.7g, 91%, 95%ee). 95%ee[Daicel Chiralcel AD-H column, n-hexane / i-PrOH=70:30, 1.0mL / min, λ=254nm, t(minor)=37.20min, t(major)=21.58min]; 1 H NMR (300MHz, DMSO-d 6 )δ7.90–7.71(m,3H),7.54–7.43(m,2H),7.19–6.99(m,5H),6.94–6.79(m,2H),6.73–6.58(m,2H),5.92( s, 1H), 4.12–3.96 (m, 1H), 3.84 (dd, J=16.3, 7.1 Hz, 1H), 3.19–3.02 (m, 2H), 2.00 (s, 3H).

Embodiment 3

[0037] Embodiment 3: Preparation of chiral benzodiazepines

[0038]Dissolve 2-(1H-indoline)aniline (10.5g, 50mmol) and 2-naphthyl pyruvate (13.2g, 60mmol) in 500mL tetrahydrofuran, and add 2-naphthyl at the 3,3' position while stirring The H8-BINOL derived phosphoramidite acid (0.4g) and Molecular sieves (35g) were reacted at 30°C for 48 hours. After the reaction was complete, the product was purified to obtain a white solid (16.5g, 90%, 95%ee). 95%ee[Daicel Chiralcel AD-H column, n-hexane / i-PrOH=70:30, 1.0mL / min, λ=254nm, t(minor)=37.20min, t(major)=21.58min]; 1 H NMR (300MHz, DMSO-d 6 )δ7.90–7.71(m,3H),7.54–7.43(m,2H),7.19–6.99(m,5H),6.94–6.79(m,2H),6.73–6.58(m,2H),5.92( s, 1H), 4.12–3.96 (m, 1H), 3.84 (dd, J=16.3, 7.1 Hz, 1H), 3.19–3.02 (m, 2H), 2.00 (s, 3H).

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 chiral benzodiazepine compound and a synthesis method thereof. The method comprises the step of reacting substituted arylamine and pyruvic acid-2-naphthyl ester under the catalysis of chiral phosphoryl imidic acid. The method disclosed by the method has the advantages that the reaction condition is mild, reaction under normal temperature is achieved, the use amount of catalysts is less, the yield is up to 90%, the enantioselectivity can reach 99%, the reaction time is short, the enantioselectivity is good, and the method can be used for high-efficiency synthesis of the chiral benzodiazepine compound.

Description

technical field [0001] The invention belongs to the technical field of synthetic chemistry, in particular to a chiral benzodiazepine Compounds and methods of their synthesis. Background technique [0002] In modern organic chemistry, benzodiazepines A series of biologically active compounds are derived from the skeleton structure. Roche discovered benzodiazepines more than half a century ago Class structure, and applied to sedation-hypnosis. Two landmark drugs, chlordiazepoxide and diazepam, were launched in 1960 and 1963, respectively. In the 1970s and 1980s, 1,4-benzodiazepines These compounds have monopolized the market for anxiety and insomnia drugs. In recent years, the preparation of chiral benzodiazepines Structured compounds began to attract people's attention. For example, the structure of cholecystokinin receptor antagonist L-365260 contains chiral benzodiazepine Backbone, and two HIV protease and hepatitis C virus NS5B polymerase inhibitors containi...

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): C07D487/06
CPCC07B2200/07C07D487/06
Inventor 张锁秦高纪罡郑良玉张广良乐成芝
Owner JILIN 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