Method for preparing praziquantel

A technology of praziquantel and pyridine, applied in the field of preparation of praziquantel, can solve the problems of complicated reaction operation, harsh reaction conditions, high price and the like, and achieve the effects of shortening the reaction process, mild reaction conditions and improving the total yield

Inactive Publication Date: 2009-06-03
SHANGHAI WANXIANG INDAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] 1. The synthesis method using diacetonitrile amine as the main raw material, relatively speaking, the raw material is relatively difficult to obtain, and the reaction conditions of each step are relatively strict, and the cost will be higher than the market price, and there is no market-oriented condition;
[0004] 2. phenylethylamine is the synthetic method of raw material, and this method can realize green production, has effectively controlled pollution, but has used raw materials such as halogenated acetaldehyde dimethyl acetal in this method synthetic route, and this raw material is expensive, makes cost relatively High, does not meet market requirements;
[0005] 3. The synthesis method using isoquinoline as a raw material is the most widely used method at present, but the steps in the production process are relatively long, the reaction operations of each step are relatively complicated, the energy consumption is large, and the cost is gradually approaching the selling price. relatively thin

Method used

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  • Method for preparing praziquantel
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  • Method for preparing praziquantel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026]

[0027] Add isoquinoline (12.9g, 0.1mol), pyridine (0.4g, 5mmol) and sodium cyanide (5.9g, 0.12mol), then add water (300ml), 1,2-dichloroethane (300ml), stir well and cool to -20°C with ice-salt water bath, then slowly add benzoyl chloride (16.2g, 0.11mol ), keep the temperature of the reaction mixture not exceeding -15°C during the dropwise addition, continue to stir the reaction at 0°C for 4 hours after the dropwise addition, then remove the ice-salt water bath, slowly rise to room temperature, then add dichloromethane (300ml ), separated the organic phase, dried with anhydrous sodium sulfate, filtered to remove the desiccant, and concentrated under reduced pressure to obtain a yellow solid as the first step product (24.6g). The yield was 92.5%. The melting point was 125-127°C.

[0028]

[0029] In the high-pressure hydrogenation reactor, add the first step product (26.6g, 0.1mol) and anhydrous methanol (600ml), then add the Ru / C catalyst (1.3g) containing 5% r...

Embodiment 2

[0033] Other steps are identical with embodiment 1, just the preparation method of A step is as follows:

[0034] Add isoquinoline (12.9g, 0.1mol), pyridine (0.4g, 5mmol) and sodium cyanide (5.4g, 0.11mol), then add water (300ml), 1,2-dichloroethane (300ml), stir well and cool to -20°C with an ice-salt water bath, then slowly add benzoyl chloride (17.7g, 0.11mol ), keep the temperature of the reaction mixture not exceeding -15°C during the dropwise addition, continue to stir the reaction at 0°C for 4 hours after the dropwise addition, then remove the ice-salt water bath, slowly rise to room temperature, then add dichloromethane (300ml ), separated the organic phase, dried with anhydrous sodium sulfate, filtered to remove the desiccant, concentrated under reduced pressure to obtain a yellow solid as the first step product (24.3g), yield 91.4%.

Embodiment 3

[0036] Other steps are identical with embodiment 1, just the preparation method of B step is as follows:

[0037] In the high-pressure hydrogenation reactor, add the first step product (26.6g, 0.1mol) and anhydrous methanol (650ml), then add the Ru / C catalyst (1.3g) containing 5% ruthenium, stir the rear airtight reactor, Pass in hydrogen until the hydrogen pressure is 4MPa, then raise the temperature to 40°C, stir and react for 6 hours, ventilate after the reaction until it reaches normal pressure, cool to room temperature, filter and recover the catalyst, concentrate the filtrate under reduced pressure and distill off anhydrous methanol, The solid precipitated, was collected and dried to obtain the second-step product (25.1 g), with a yield of 92.3%. The next step reaction could be carried out directly without further purification.

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Abstract

The invention relates to a method for preparing praziquantel, which is characterized by comprising the steps: (1) isoquinolin, sodium cyanide or potassuim cyanide and triethylamine or pyridine are added into a reactor to react, and yellow solid which is a first step product is obtained; (2) the first step product is added into a high-pressure hydrogenation kettle and filled with hydrogen to react under the action of catalyst, so that a second step product is obtained; (3) after being stirred and dissolved, the second step product and ethyl acetate is added with anhydrous potassium carbonate or anhydrous sodium carbonate, and then is stirred at the room temperature and dripped with chloracetyl chloride to be stirred at the room temperature to react, so that the solid obtained in the reaction is crude product of the praziquantel, and fine product is obtained by recrystallization of absolute methanol. Compared with the prior art, the method has the advantages of shortening the reaction process, reducing the energy consumption, improving the overall yield, etc.

Description

technical field [0001] The invention relates to a pharmaceutical intermediate, in particular to a preparation method of praziquantel. Background technique [0002] Regarding the synthesis of praziquantel, there are mainly the following three methods now: [0003] 1. The synthesis method using diacetonitrile amine as the main raw material, relatively speaking, the raw material is relatively difficult to obtain, and the reaction conditions of each step are relatively strict, and the cost will be higher than the market price, and there is no market-oriented condition; [0004] 2. phenylethylamine is the synthetic method of raw material, and this method can realize green production, has effectively controlled pollution, but has used raw materials such as halogenated acetaldehyde dimethyl acetal in this method synthetic route, and this raw material is expensive, makes cost relatively High, does not meet market requirements; [0005] 3. The synthesis method using isoquinoline as...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04
Inventor 蒋中良
Owner SHANGHAI WANXIANG INDAL
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