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Preparation method for levo-praziquantel

A technology of L-praziquantel and praziquantel amine, which is applied in the field of preparation of antiparasitic drugs, can solve the problems of long synthetic process route, harsh reaction conditions, and high impurity content, and achieve improved yield, purity, and good stability , The effect of simple process operation

Active Publication Date: 2013-12-04
SHAOXING MINSHENG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In the traditional production process of praziquantel, it is necessary to use some toxic and harmful chemical substances, such as potassium cyanide, etc. In addition, its synthetic process route is long, and the reaction conditions are relatively harsh, and the final product yield is very low, and the impurity content higher

Method used

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  • Preparation method for levo-praziquantel

Examples

Experimental program
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Effect test

Embodiment 1

[0052] A preparation method of L-praziquantel, carried out according to the following steps:

[0053] (1) Add 95g of praziquantel amine phosphate, 900g of isopropanol and 245g of water in sequence in a 1000mL three-necked flask equipped with a reflux condenser, a thermometer, and a magnetic stirring device, and dissolve. Add 85g of sodium hydroxide solution (30% by weight) dropwise, stir for 1 hour, cool to 10°C and filter;

[0054] (2) Add 73g of isopropanol solution of L-dibenzoyltartaric acid to the filtrate, add 200g of isopropanol, heat to dissolve and clarify, slowly cool to 20°C, continue stirring for 10h, and centrifuge to obtain L-praquine Ketoamine tartrate crude product 47 g, HPLC purity: 99.93%, ee%: 98.12%;

[0055] (3) Add 47g of crude L-praziquantel amine tartrate to a mixed solution of 506g of isopropanol and 202g of pure water, heat until completely dissolved, slowly cool to 20°C, continue to stir for 10h, and centrifuge to obtain L-praziquantel Amine tartra...

Embodiment 2

[0066] A kind of preparation method of L-praziquantel of the present embodiment is carried out according to the following steps:

[0067] (1) In a 5000mL three-neck flask equipped with a reflux condenser, a thermometer and a magnetic stirring device, add 481g of praziquantelamine phosphate, 4500g of isopropanol and 1225g of water in sequence to dissolve. Add 425g of sodium hydroxide solution (30% by weight) dropwise, stir for 1 hour, cool to 10°C and filter;

[0068] (2) Add 370g of the isopropanol solution of L-dibenzoyltartaric acid to the filtrate, add 1000g of isopropanol, heat to dissolve and clarify, slowly cool to 20°C, continue to stir for 10h, and centrifuge to obtain L-praziquine Ketoamine tartrate 47 g, HPLC purity: 99.93%, ee%: 98.12%;

[0069] (3) Add 238g of the crude product of L-praziquantel amine tartrate into a mixed solution of 2560g of isopropanol and 1024g of pure water, heat until completely dissolved, slowly cool at 20°C, continue to stir for 10h, and c...

Embodiment 3

[0075] A kind of preparation method of L-praziquantel of the present embodiment, other steps are identical with embodiment 2, just the basic compound of step (4) is triethylamine:

[0076] Add 194g of L-praziquantel amine tartrate to 1100g of dichloromethane; under stirring, add 100g of triethylamine dropwise, after the dropwise addition, stir for 30min, cool to below 7°C and dropwise add cyclohexanoyl chloride (51.4g) After a solution of dichloromethane (200g) was reacted at 3-5°C for 2h, the reaction was complete as detected by TLC. The stirring was turned off, and the layers were separated. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 110 g of crude L-praziquantel.

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Abstract

The invention relates to a preparation method for levo-praziquantel. The method includes the following steps that under the alkaline condition, a praziquantel amine phosphate compound serves as original raw material and is resolved by tartaric acid and derivatives of the tartaric acid, and the obtained levo-praziquantel amine tartrate compound is subjected to recrystallization; in the presence of an alkali compound, a hexamethylene formylation reaction is carried out on the recrystallized levo-praziquantel amine tartrate compound obtained and cyclohexanecarboxylic acid chloride to obtain a levo-praziquantel crude product, and the refined levo-praziquantel is obtained through decoloration, filtration, and filtrate recrystallization. The preparation method for the levo-praziquantel shortens a technological process, reduces generation of by-products and improves the quality and yield of the product. Recovered praziquantel amine compounds of the other configuration can be recycled after racemization, the resolving agent can be used repeatedly, and pollution to the environment is effectively reduced.

Description

technical field [0001] The invention relates to a preparation method of an antiparasitic drug, in particular to a preparation method of L-praziquantel. Background technique [0002] Praziquantel, also known as ciclopraziquantel, is a broad-spectrum antiparasitic drug. It has a wide anti-helminth spectrum, has killing effects on lung fluke, schistosomiasis, clonorchis sinensis, hydatid, cysticercosis Sparganum monstii, etc., and has small toxic and side effects. The effect of praziquantel is characterized by high curative effect and short course of treatment. , small dose, fast metabolism, low toxicity and convenient oral administration. The advent of praziquantel is a major breakthrough in the chemotherapy of parasitic diseases, and now it has become the drug of choice for the treatment of many parasitic diseases. [0003] Praziquantel was first synthesized by Seubere et al. in 1975, and the German E-merck and Bayer two pharmaceutical factories successfully developed the d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04
Inventor 岳从永罗金表
Owner SHAOXING MINSHENG PHARMA
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