Improved synthesis process for lamotrigine

A synthesis process and lamotrigine technology are applied in the field of improved lamotrigine synthesis technology, which can solve problems such as affecting the yield of product lamotrigine, and achieve the effect of improving quality and yield

Active Publication Date: 2016-11-09
ZHEJIANG QICAI ECO TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in this process, the condensation of the aminocarbonyl group will generate a molecule of water, and the neutralization of the bicarbonate aminoguanidine salt will also generate a molecule of water. The inorganic acid solution will bring part of the water, causing water to be brought into the reaction system, seriously affecting The yield of product lamotrigine, therefore improving the yield of this step reaction will have great economic prospect

Method used

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  • Improved synthesis process for lamotrigine
  • Improved synthesis process for lamotrigine
  • Improved synthesis process for lamotrigine

Examples

Experimental program
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Effect test

Embodiment 1

[0030] A kind of improved lamotrigine synthetic technique, concrete implementation steps are as follows:

[0031] (1) Synthesis of 2,3-dichlorobenzoyl cyanide: Add 50g of 2,3-dichlorobenzoic acid and 50g of thionyl chloride into a 500ml four-necked bottle, react for 6h to the end, and distill the chlorinated solution under reduced pressure sulfoxide, then add 30g of cuprous cyanide, carefully raise the temperature to 160°C, react for 6h to the end of the reaction, filter out the solid, and get 2,3-dichlorobenzoyl cyanide solution;

[0032] (2) Condensate preparation: add 40g of aminoguanidine carbonate and 200ml of methanol (zeotropic agent) into the reactor, stir and add 30g of concentrated sulfuric acid dropwise, after the addition is completed, the azeotropic agent is evaporated, and water is taken out, and suction filtered , the solid was put into the reaction bottle, stirred at 80°C and vacuum-dried. Add the 2,3-dichlorobenzoyl cyanide solution obtained in step (1), rais...

Embodiment 2

[0041] A kind of improved lamotrigine synthetic technique, concrete implementation steps are as follows:

[0042] (1) Synthesis of 2,3-dichlorobenzoyl cyanide: add 500g of 2,3-dichlorobenzoic acid and 500g of thionyl chloride to the reactor, react for 6h to the end, and distill the thionyl chloride under reduced pressure , then add 30g of cuprous cyanide, carefully raise the temperature to 160°C, react for 6h to the end of the reaction, filter off the solid, and get 2,3-dichlorobenzoyl cyanide solution;

[0043] (2) Condensate preparation: Add 400g of aminoguanidine carbonate and 2L of methanol into the reactor, stir and add 300g of concentrated sulfuric acid dropwise, the entrainer is evaporated after the addition is completed, and the water is taken out, suction filtered, and the solid enters the reaction bottle , stirred at 80°C and dried under reduced pressure. Add the 2,3-dichlorobenzoyl cyanide solution obtained in step (1), raise the temperature to 80°C and react for 3...

Embodiment 3

[0047] A kind of improved lamotrigine synthetic technique, concrete implementation steps are as follows:

[0048] (1) Synthesis of 2,3-dichlorobenzoyl cyanide: Add 1kg of 2,3-dichlorobenzoic acid and 0.5kg of thionyl chloride to the reactor, react for 7h to the end, and distill the oxychloride under reduced pressure sulfone, then add 0.5kg cuprous cyanide, carefully raise the temperature to 160°C, react for 6h to the end of the reaction, filter out the solid, and get 2,3-dichlorobenzoyl cyanide solution;

[0049] (2) Condensate preparation: Add 0.8kg aminoguanidine carbonate and 3.5L toluene into the reactor, stir and add 0.6kg concentrated sulfuric acid dropwise, after the dropwise addition is completed, the entrainer is evaporated, and water is taken out, suction filtered, solid into the reaction flask, stirred at 80°C and vacuum-dried. Add the 2,3-dichlorobenzoyl cyanide solution obtained in step (1), raise the temperature to 80°C and react for 4 hours to the end of the re...

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Abstract

The invention discloses an improved synthesis process for lamotrigine. The process comprises the following steps: (1) synthesizing 2,3-dichlorobenzoyl cyanide: adding 2,3-dichlorobenzoic acid and thionyl chloride into a reactor, carrying out depressurized evaporating to remove thionyl chloride after a reaction is completed, adding cuprous cyanide into the reactor, and filtering out solids after a reaction is completed, so as to obtain a 2,3-dichlorobenzoyl cyanide solution; (2) preparing a condensate: adding aminoguanidine carbonate and an entrainer into a reactor, dropwise adding concentrated sulfuric acid, distilling off the entrainer and water, carrying out suction filtration, enabling solids to enter a reaction bottle, carrying out depressurized pumping, then, adding the 2,3-dichlorobenzoyl cyanide solution obtained in the step (1) into the reaction bottle, cooling the reaction bottle to room temperature after a reaction is completed, and carrying out suction filtration, so as to obtain the condensate; and (3) preparing cyclics: adding liquid alkali into the condensate obtained in the step (2), and carrying out crystallizing, filtering, washing and baking after a reaction, thereby obtaining the lamotrigine. According to the improved synthesis process for the lamotrigine, the quality and yield of the product, i.e., the lamotrigine can be remarkably increased, and the yield reaches 90% or more.

Description

technical field [0001] The invention relates to the field of medicine synthesis technology, in particular to an improved synthesis technology of lamotrigine. Background technique [0002] Lamotrigine, scientific name 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine, is a new type of specific epilepsy drug. It has been clinically proven that at the same dose, the drug is confirmed to have no sedative effect. Compared with traditional antiepileptic drugs, the incidence and severity of adverse reactions are significantly reduced. As a new generation of specific antiepileptic drugs, Not only has the exact and broad-spectrum antiepileptic effect, but also has low toxicity, easy tolerability, and small side effects. Its structural formula is as follows: [0003] [0004] The patent with the publication number CN 102766104 discloses a synthetic method of lamotrigine, which uses 2-(2,3-dichlorophenyl)-2-(guanidine imino)acetonitrile cyclization to generate lamotrigine , the p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D253/075
CPCC07D253/075
Inventor 金城陈丽娜梁伟张通陈磊
Owner ZHEJIANG QICAI ECO TECH CO LTD
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