Supercharge Your Innovation With Domain-Expert AI Agents!

Praziquantel impurity A and preparation method thereof

A technology of praziquantel and impurities, which is applied in the field of organic compound synthesis, and can solve problems such as low conversion rate and cumbersome operation steps

Inactive Publication Date: 2021-05-11
山东药品食品职业学院
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the synthesis method of praziquantel impurity A in the prior art has the disadvantages of low conversion rate and complicated operation steps

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
  • Praziquantel impurity A and preparation method thereof
  • Praziquantel impurity A and preparation method thereof
  • Praziquantel impurity A and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] S11. Add 100mL of water and 50mL of concentrated ammonia water to a 500mL autoclave, control the pH of the system to 10, add 40g of praziquantel, and heat up to 80°C under 0.01Mpa for reflux reaction for 5h, then cool down after the reaction to 10°C, release the pressure to obtain a feed liquid containing intermediate D;

[0049] S12. Use dichloromethane to extract three times, each time using 200mL, combine the dichloromethane layers, and use a rotary evaporator to evaporate to dryness at 40°C to obtain 1,2,3,6,7,11b-hexahydropyrazino[ 2,1-α]isoquinolin-4-one intermediate D;

[0050] S13. Add 24.0g of intermediate D to a 500mL reaction flask, add 150g of dichloromethane, add 12g of triethylamine, and add 15.0g of benzoyl chloride dropwise at 25°C. Continue to react for 3h under the condition;

[0051] S14. Add 150 mL of water to the solution after the reaction in step S13 and stir for 20 minutes, then add hydrochloric acid dropwise to adjust the pH to 2, and let stan...

Embodiment 2

[0055] S21. Add 100mL of water and sodium hydroxide to a 500mL autoclave, and control the pH value of the system to 10, add 40g of praziquantel, and raise the temperature to 80°C under the condition of 0.01Mpa, heat and reflux for 5h, after the reaction is completed Cool down to 10°C, release the pressure to obtain a feed liquid containing intermediate D;

[0056] S22. Use ethyl acetate to extract three times, each time 250 mL, combine the ethyl acetate layers, and use a rotary evaporator to evaporate to dryness at 55 ° C to obtain 1,2,3,6,7,11b-hexahydropyrazino[ 2,1-α]isoquinolin-4-one intermediate D;

[0057] S23. Add 23.2g of intermediate D to a 500mL reaction flask, add 170g of ethyl acetate, add 12g of triethylamine, and add 15.0g of benzoyl chloride dropwise at 25°C. Continue to react for 3h under the condition;

[0058] S24. Add 150 mL of water to the solution after the reaction in step S23 and stir for 20 minutes, then add sulfuric acid dropwise to adjust the pH to ...

Embodiment 3

[0062] S31. Add 100mL of water and 45mL of concentrated ammonia water to a 500mL autoclave, and control the pH of the system to 9, add 40g of praziquantel, and raise the temperature to 90°C under 0.02Mpa for reflux reaction for 3h. After the reaction is completed Cool down to 20°C, release the pressure to obtain a feed liquid containing intermediate D;

[0063] S32. Extract three times with dichloromethane, each time 200 mL, combine the ethyl acetate layers, and evaporate to dryness at 45° C. with a rotary evaporator to obtain 1,2,3,6,7,11b-hexahydropyrazino[ 2,1-α]isoquinolin-4-one intermediate D;

[0064] S33. Add 24.5g of intermediate D to a 500mL reaction flask, add 160g of dichloromethane, add 11g of triethylamine, and add 12.6g of benzoyl chloride dropwise at 25°C. Continue to react for 3h under the condition;

[0065] S34. Add 150 mL of water to the solution after the reaction in step S33 and stir for 40 minutes, then add hydrochloric acid dropwise to adjust the pH to...

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 relates to the technical field of organic matter synthesis, in particular to a praziquantel impurity A and a preparation method thereof. The method comprises the steps of accindg praziquantel into an alkaline aqueous solution for heating reflux to obtain a 1,2,3,6,7,11b-hexahydropyrazino[2, 1-alpha]isoquinolin-4-one intermediate D; adding organic alkali and benzoyl chloride into the solution of the intermediate D, adding water after reaction, and conducting standing for layering; and carrying out reduced pressure evaporation on the organic layer to dryness, and sequentially carrying out redissolution, stirring crystallization, filtration and drying to obtain the praziquantel impurity A. The intermediate D is prepared through hydrolysis of praziquantel under the alkaline condition, and the intermediate D is good in stability and beneficial for reducing generation of by-products in chemical reaction, so that the yield and purity of the product are effectively improved; and in the benzoylation reaction, the organic alkali is introduced to continuously promote the forward proceeding of the reaction, the whole reaction is carried out at normal temperature without harsh reaction conditions, the generated ammonium salts can be directly recycled, and the emission of wastes and the pollution to the environment are reduced.

Description

technical field [0001] The invention relates to the technical field of organic compound synthesis, in particular to a praziquantel impurity A and a preparation method thereof. Background technique [0002] Praziquantel, chemical name 2-(cyclohexyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one , is a broad-spectrum and high-efficiency anthelmintic drug, mainly used for the treatment of schistosomiasis and tapeworms, especially effective for schistosomiasis, Chinese liver fluke, and Schizophrenia grandis, which are recorded in Chinese Pharmacopoeia, American Pharmacopoeia and European Pharmacopoeia . [0003] The structural formula of praziquantel is as follows: [0004] [0005] At present, the commonly used synthesis method is to obtain isoquinoline as raw material, chlorinated addition reaction with benzyl chloride and potassium cyanide, hydrogenation reduction transposition reaction, chloroacetyl ring closure reaction, hydrolysis cyclohexane formylation...

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): C07D471/04
CPCC07D471/04
Inventor 李振兴单雪梅丁晓红邹小丽袁万瑞李伟李光跃
Owner 山东药品食品职业学院
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com