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

Electrochemical preparation method of rasagiline and Pevonedistat intermediates

An intermediate and electrode technology, applied in the field of electroreduction preparation, can solve the problems of large environmental pollution, excessive heavy metals, affecting the purity of intermediates, etc., and achieve the effects of simplifying the process flow, suitable for large-scale popularization and application, and reducing production costs.

Pending Publication Date: 2022-05-06
HUNAN UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The preparation of 2,3-dihydro-1H-indene-1-amine Ⅰ adopts catalytic hydrogenation method: the catalyst palladium is more expensive; the catalyst palladium or nickel and the reduction product - the amino compound intermediate form a complex that is difficult to separate, which affects the Purity of intermediates and excessive heavy metals in anti-Parkinson drugs and Pevonedistat, a drug for treating high-risk myelodysplastic syndromes
Preparation of 2,3-dihydro-1H-indene-1-amine Ⅰ by reduction of inorganic reducing agent zinc powder, metal nickel aluminum alloy (Raney nickel) and aluminum amalgam, difficult post-treatment, large amount of waste water, and great environmental pollution ; especially mercury, which is highly toxic

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
  • Electrochemical preparation method of rasagiline and Pevonedistat intermediates
  • Electrochemical preparation method of rasagiline and Pevonedistat intermediates
  • Electrochemical preparation method of rasagiline and Pevonedistat intermediates

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Preparation of 2,3-Dihydro-1H-inden-1-amine by Electroreduction

[0044]

[0045] Divided electrolyzer ( figure 1 ), using a proton exchange membrane. At the cathode (zinc sheet 2×2cm 2) room, add 0.44g (3mmol) 2,3-dihydro-1H-inden-1-one oxime, 10mL methanol and 40mL0.2 mol / L KOH, anode room (platinum mesh 1×1cm 2 ) 50mL KOH solution with a concentration of 5mol / L; 50℃ constant current 0.6A reaction, current density 0.15A / cm 2 , the saturated calomel electrode is used as a reference electrode to monitor the cathode reaction potential, the cathode potential is 7.0-15.0V, the electroreduction reaction is 6.5h, the catholyte is extracted with ethyl acetate for 3 times, the organic layer is collected and dried over anhydrous sodium sulfate, and spin-evaporated to remove the solvent. An oily compound was obtained, which was formed into a salt by injecting HCl gas to obtain 0.46 g of 2,3-dihydro-1H-inden-1-amine hydrochloride (white solid), melting point 210-212°C, yiel...

Embodiment 2

[0047] Preparation of 2,3-Dihydro-1H-inden-1-amine by Electroreduction

[0048]

[0049] Divided electrolyzer ( figure 1 ), using a proton exchange membrane. At the cathode (zinc sheet 2×2cm 2 ) room, add 0.88g (6mmol) 2,3-dihydro-1H-inden-1-one oxime, 5mL methanol: 45mL0.5 mol / LKOH, anode room (platinum mesh 1×1cm 2 ) 50mL KOH solution with a concentration of 5mol / L; 55℃ constant current 0.6A reaction, current density 0.15A / cm 2 , the saturated calomel electrode is used as a reference electrode to monitor the cathode reaction potential, the cathode potential is 7.0-15.0V, the electroreduction reaction is 6.5h, the catholyte is extracted with ethyl acetate for 3 times, the organic layer is collected and dried over anhydrous sodium sulfate, and spin-evaporated to remove the solvent. The oily compound was obtained, and HCl gas was added to form a salt to obtain 0.92 g of 2,3-dihydro-1H-inden-1-amine hydrochloride (white solid), melting point 210-212°C, yield 90.6%.

Embodiment 3

[0050] Embodiment 3 (control experiment 1)

[0051] Reduction Preparation of 2,3-Dihydro-1H-inden-1-amine

[0052]

[0053] 2,3-Dihydro-1H-indene-1-amine was prepared according to the literature [Research on the synthesis process of the second generation monoamine oxidase inhibitor rasagiline mesylate [D]. Jilin University, 2018] method: 50.0g (0.34mol ) 2,3-dihydro-1H-inden-1-one oxime, 250mL of ethanol, add 150g of 20% NaOH aqueous solution, control the reaction temperature at 60-65°C, add 100g of nickel-aluminum alloy in batches, and control the addition time within 2h; After the addition, maintain the temperature at 60-65°C for 6 hours. Suction filtration after completion of the reaction, the obtained solution was extracted three times with dichloromethane, the organic phase was washed with water, the dichloromethane was concentrated to about half of the remaining volume, extracted twice with 4mol / L hydrochloric acid solution, the combined feed liquid was concentrated ...

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

PropertyMeasurementUnit
concentrationaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to an electroreduction preparation method of an intermediate 2, 3-dihydro-1H-indene-1-amine (I) of an anti-Parkinson drug rasagiline and a drug Pevonedistat for treating a high-risk myelodysplastic syndrome, and a preparation method of the intermediate 2, 3-dihydro-1H-indene-1-amine (I). The preparation reaction comprises the following steps: in a separated electrolytic cell, forming a cathode electrolyte by using an alkaline solution of 2, 3-dihydro-1H-indene-1-ketoxime (A) and an organic solvent; the anolyte is an alkaline solution; and carrying out an electroreduction reaction to obtain a cathode electrolysis product of the 2, 3-dihydro-1H-indene-1-amine (I).

Description

technical field [0001] The present invention relates to a new method for the electroreduction preparation of an intermediate of the anti-Parkinson drug rasagiline mesylate and the drug Pevonedistat for the treatment of high-risk myelodysplastic syndromes, specifically 2,3-dihydro-1H-inden-1-one Preparation of 2,3-dihydro-1H-inden-1-amine and its hydrochloride by electroreduction of oxime. Background technique [0002] Rasagiline mesylate is a monoamine oxidase B (MAO-B) inhibitor jointly developed by Teva Company of Israel and Lundbeck Company of Denmark. It can effectively treat early Parkinson's disease by blocking the decomposition of neurotransmitter dopamine. PD, rasagiline, as the second generation MAO-B selective inhibitor following selegiline, is superior to selegiline in terms of effectiveness, side effects, and neuroprotection, and was approved in February 2005. Launched in Europe and approved by the US FDA. [0003] The preparation method of rasagiline mesylate:...

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): C25B3/25C25B3/09
CPCC25B3/25C25B3/09
Inventor 胡艾希王曼易阳杰叶姣
Owner HUNAN 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