Method for synthesizing praziquantel from praziquantel impurity B

Abstract

The invention discloses a method for synthesizing praziquantel from a praziquantel impurity B. The method belongs to the technical field of medicine and chemical engineering, and is characterized by comprising the following steps: firstly, adding the praziquantel impurity B, a certain amount of process water, metal powder or strip-shaped metal into an organic solvent A, then controlling the temperature to be 40-60 DEG C, dropwise adding acid, after dropwise adding, keeping the temperature for 2 hours, and then, carrying out solid-liquid separation to obtain the praziquantel impurity B; the method has the advantages that the impurity B of the praziquantel is directly converted into the praziquantel, the problem that the impurity B in the praziquantel exceeds the standard and cannot be purified is solved, the purity of the praziquantel is improved at low cost, the operation is simple, the reaction is mild, the toxicity is low, the risk is small, and the requirements of industrial mass production are met.

Description

Technical Field

[0001] The present application relates to the field of medicine and chemical technology, and more specifically to a method for synthesizing praziquantel from praziquantel impurity B. Background Art

[0002] Praziquantel is a synthetic pyrazine isoquinoline derivative, which is recognized worldwide as a highly effective and broad-spectrum antiparasitic drug. It is widely used to treat diseases such as Schistosoma japonicum, Schistosoma haematobium, Schistosoma mansoni, Clonorchiasis, Paragonimiasis, Sparganosis mengidioidomyces, Fasciola zingiberensis, Echinococcosis, Tapeworms and Cysticercosis. In addition, it has the advantages of a broad antiparasitic spectrum, high efficacy, low toxicity, short course of treatment and easy use. In addition to being used in humans, it is also widely used in antiparasitic treatment of animals, poultry, etc. Praziquantel is the preferred drug for the treatment of various parasitic diseases on the market. The chemical structure of praziquantel is as follows:

[0003]

[0004] At present, the synthetic route of industrial production of praziquantel at home and abroad generally adopts the direct method, which not only has fewer production steps, but also has mature methods and processes and readily available raw materials. However, since the impurity B of praziquantel often exceeds the standard during the production process, and the impurity cannot be purified by crystallization, many unqualified products appear in the production process, resulting in increased production costs. Therefore, the process for preparing praziquantel in the prior art has defects and shortcomings that are not suitable for large-scale industrial production.

[0005] In view of this, the present inventors designed a method for synthesizing praziquantel from praziquantel impurity B. Summary of the invention

[0006] In view of the shortcomings of the prior art, the object of the present invention is to provide a method for synthesizing praziquantel from praziquantel impurity B, which has the advantages of simple operation, high yield and high efficiency, and is suitable for large-scale and industrial preparation of high-purity praziquantel to meet the requirements of industrial production of praziquantel.

[0007] To achieve the above object, the present invention provides the following technical solution: a method for synthesizing praziquantel from praziquantel impurity B, comprising the following steps:

[0008] S1. Add praziquantel impurity B, process water, and metal to organic solvent A, and control the temperature to 40-60 ° C, then add acid dropwise, and then keep warm for 2 hours;

[0009] S2. After keeping warm for 2 hours in step S1, washing with water was added, followed by filtration, washing with water, and then drying to obtain praziquantel;

[0010] The reaction equation is as follows:

[0011]

[0012] Preferably, in step S1, the organic solvent A is any one of methanol and ethanol.

[0013] Preferably, in step S1, the metal object is any one of zinc powder, iron powder and magnesium chips.

[0014] Preferably, the metal object is in powder or strip form.

[0015] Preferably, in step S1, the acid solution is any one of hydrochloric acid and acetic acid.

[0016] Preferably, in step S1, the molar ratio of the acid solution: the metal object: the praziquantel impurity B is 4-8:2-4:1.

[0017] In summary, the present invention has the following advantages:

[0018] The preparation method of the present invention is simple to operate, and can realize direct conversion of the impurity B of praziquantel into praziquantel, thereby solving the problem that the impurity B exceeds the standard in praziquantel and cannot be purified. The method has high yield and high efficiency, low cost, improved purity of praziquantel, mild reaction, low toxicity, and low danger, and meets the requirements of large-scale industrial production, and has significant application value. DETAILED DESCRIPTION

[0019] The technology of the present invention is further described below in conjunction with specific examples.

[0020] Example 1

[0021] A method for synthesizing praziquantel from praziquantel impurity B comprises the following steps:

[0022] In a 500ml four-necked reaction flask, 100ml of methanol, praziquantel impurity B (31g, 0.1mol), 50ml of process water, and zinc powder (13g, 0.2mol) were added. Then, the temperature of the 500ml four-necked reaction flask was controlled at 50-55°C, and 36% hydrochloric acid (40.56g, 0.4mol) was added dropwise. After the addition was completed, the mixture was kept warm for 2 hours. Then, 50ml of process water was added to the organic layer and stirred for 30 minutes. The mixture was directly filtered, and then washed with process water until it was neutral. Finally, the mixture was dried to obtain praziquine (29.6g, 0.09487mol) with a purity of more than 99.5% and impurity B less than 0.05%.

[0023] Example 2

[0024] A method for synthesizing praziquantel from praziquantel impurity B comprises the following steps:

[0025] In a 500ml four-necked reaction flask, 100ml of ethanol, praziquantel impurity B (31g, 0.1mol), 50ml of process water, and iron powder (16.8g, 0.3mol) were added. Then, the temperature of the 500ml four-necked reaction flask was controlled at 55-60°C, and acetic acid (36g, 0.6mol) was added dropwise. After the addition was completed, the mixture was kept warm for 2 hours. Then, 50ml of process water was added to the organic layer and stirred for 30 minutes. The mixture was directly filtered, and then washed with process water until it was neutral. Finally, the mixture was dried to obtain praziquine (29.7g, 0.09519mol) with a purity of more than 99.5% and impurity B less than 0.05%.

[0026] Example 3

[0027] A method for synthesizing praziquantel from praziquantel impurity B comprises the following steps:

[0028] In a 500ml four-necked reaction flask, 100ml of methanol, praziquantel impurity B (31g, 0.1mol), 50ml of process water, and magnesium chips (7.29g, 0.3mol) were added. Then, the temperature of the 500ml four-necked reaction flask was controlled at 50-55°C, and acetic acid (36g, 0.6mol) was added dropwise. After the addition was completed, the mixture was kept warm for 2 hours. Then, 50ml of process water was added to the organic layer and stirred for 30 minutes. The mixture was directly filtered, washed with process water until neutral, and finally dried to obtain praziquine (29.4g, 0.09423mol) with a purity of more than 99.5% and impurity B less than 0.05%.

[0029] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the design concept of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing praziquantel from praziquantel impurity B, characterized in that: The following steps are included: S1. Add praziquantel impurity B, process water, and metal to organic solvent A, and control the temperature to 40-60 ° C, then add acid dropwise, and then keep warm for 2 hours; S2. After keeping warm for 2 hours in step S1, washing with water was added, followed by filtration, washing with water, and then drying to obtain praziquantel; The reaction equation is as follows:

2. The method for synthesizing praziquantel from praziquantel impurity B according to claim 1, characterized in that: In step S1, the organic solvent A is any one of methanol and ethanol.

3. The method for synthesizing praziquantel from a praziquantel impurity B according to claim 1, characterized in that: In step S1, the metal object is any one of zinc powder, iron powder and magnesium chips.

4. The method for synthesizing praziquantel from praziquantel impurity B according to claim 3, characterized in that: The metal object is in powder or strip form.

5. The method for synthesizing praziquantel from a praziquantel impurity B according to claim 1, characterized in that: In step S1, the acid solution is any one of hydrochloric acid and acetic acid.

6. The method for synthesizing praziquantel from a praziquantel impurity B according to claim 1, characterized in that: In step S1, the molar ratio of the acid solution: the metal object: the praziquantel impurity B is 4-8:2-4:1.

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