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Method for preparing praziquantel

A technology of praziquantel and intermediates, applied in the direction of organic chemistry, etc., can solve the problems of unsuitable industrial production, high production cost and high price, and achieve the effects of low cost, good operability and safe feeding method

Inactive Publication Date: 2014-04-23
JIANGSU CHENGXIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the biggest disadvantage of this process is that the price of aminoacetaldehyde dimethyl acetal is high, and the production cost is higher than that of the original isoquinoline process, which makes this process unable to be industrialized.

Method used

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  • Method for preparing praziquantel
  • Method for preparing praziquantel
  • Method for preparing praziquantel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Add 124.6g (1mol) of chloroacetaldehyde dimethyl acetal and 1280g of 20% ammonia solution to the autoclave, raise the temperature of the reaction to 135-140°C, stir the reaction for 3 hours, distill the reaction solution, and recover the ammonia water until no obvious fraction distills. Until it comes out, weigh 110g of 40% liquid caustic soda aqueous solution and add it to the remaining reaction solution, adjust the pH of the reaction solution to 12-14, distill under reduced pressure, collect 70g of colorless and transparent liquid, and obtain the key raw material aminoacetaldehyde dimethyl acetal, which is used for Intermediate 2 was prepared.

[0032] In the reaction flask, add 24.2g (0.2mol) β-phenylethylamine, 100ml methylene chloride and 60g (0.11mol) 20% Na 2 CO 3 Aqueous solution, stir the mixture until uniform, slowly add 22.6g (0.20mol) of chloroacetyl chloride dropwise under temperature control at -5-0°C, after the addition is complete, continue to control t...

Embodiment 2

[0037] Add 124.6g (1mol) of chloroacetaldehyde dimethyl acetal and 1150g of 30% ammonia solution (20mol) in the autoclave, the reaction is heated up to 135-140°C, stirred for 3 hours, the reaction solution is distilled, and ammonia water is recovered until no Until the obvious fraction evaporates, weigh 110g of 40% liquid caustic soda aqueous solution and add it to the remaining reaction solution, adjust the pH of the reaction solution to 12-14, distill at normal pressure, collect 90g of colorless transparent liquid, and obtain the key raw material aminoacetaldehyde dimethyl acetal , used directly to prepare intermediate 2

[0038] Add 24.2gβ-phenylethylamine (0.2mol), 100ml toluene and 220g10% K in the reaction flask 2 CO 3 (0.16mol) aqueous solution, stir the mixture until uniform, slowly add 56.5g (0.50mol) chloroacetyl chloride dropwise under temperature control at -5-0°C, after the addition is complete, continue to control the temperature and stir for 3 hours, then separ...

Embodiment 3

[0043] Add 124.6g (1mol) chloroacetaldehyde dimethyl acetal and 800g40% ammonia solution (18.8mol) in the autoclave, the reaction is warmed up to 135-140 ° C, stirred for 3 hours, the reaction solution is distilled, and the ammonia is recovered until Until no obvious fractions are distilled out, weigh 110g of 40% liquid caustic soda solution and add it to the remaining reaction solution, adjust the pH of the reaction solution to 12-14, distill the solution under normal pressure, collect 92g of colorless transparent liquid, and obtain the key raw material aminoacetaldehyde Dimethyl acetal, ready for the preparation of intermediate 2.

[0044] Add 24.2gβ-phenylethylamine (0.2mol), 100ml methylene chloride and 83g20% K in the reaction flask 2 CO 3 (0.12mol) aqueous solution, stir the mixture until uniform, slowly add 18.0g (0.16mol) chloroacetyl chloride dropwise at -5-0°C under control of the temperature, after the addition is complete, continue to control the temperature and sti...

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Abstract

The invention relates to a method for preparing praziquantel, which is a one-pot method and comprises the following steps: performing an ammonolysis reaction of chloroacetaldehyde dimethyl acetal and an ammonia aqueous solution to generate aminoacetaldehyde dimethyl acetal; performing a condensation reaction of beta-phenylethylamine and chloroacetyl chloride in an organic solvent in alkaline environment to generate an intermediate 1; performing a condensation reaction of the intermediate 1 and the aminoacetaldehyde dimethyl acetal in an organic solvent to generate an intermediate 2; performing cyclization of the intermediate 2 in the presence of an acidic catalyst to generate an intermediate 3; performing a reaction of the intermediate 3 and cyclohexanecarboxylic acid chloride in an organic solvent in alkaline environment, and performing solvent crystallization to obtain the target product of praziquantel.

Description

technical field [0001] The technology of the invention relates to the technical fields of medicine and chemical industry. Background technique [0002] Praziquantel (chemical name: 2-cyclohexylformyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-α]isoquinolin-4-one), The structural formula is: [0003] [0004] Praziquantel is a broad-spectrum anti-parasitic drug, which is very effective against major human schistosomiasis. Since it was first launched in Germany in 1980, it has quickly become the first choice drug for the treatment of schistosomiasis and various parasitic diseases in the world. At present, it has become the most widely used antiparasitic drug in the world. [0005] For a long time, the production of praziquantel at home and abroad has been using the old technology of German Bayer company. This technological step is longer, has 7-8 step reaction, and yield is lower, only about 15%; Will use the highly poisonous and high pollutants such as cyanide, cyclohexane...

Claims

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Application Information

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IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 许刘华刘明明邢将军刘加根
Owner JIANGSU CHENGXIN PHARMA
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