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Olsalazine sodium and preparation method thereof

A technology for olsalazine sodium and sodium nitrite, which is applied to the field of olsalazine sodium and its preparation, can solve the problems of high impurities in crude products, low product purity, and many side reactions, and achieves guaranteed reaction concentration, avoided side reactions, and guaranteed effect of speed

Inactive Publication Date: 2018-02-16
上海泰坦科技股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, in actual production, there are still many deficiencies in this process, especially the coupling reaction of diazotization, that is, using 3-amino-6-methanesulfonyloxy-methyl benzoate as raw material to generate 2-hydroxyl-5-[ (4-methanesulfonyl oxygen-3-methoxycarbonylphenyl)-azo]-methyl benzoate (hereinafter referred to as coupling) step, the side reaction of this step reaction is more, crude product impurity is many, and product purity is low , the content of individual impurities is even greater than 2%; the total yield is only about 50%, and it needs multiple refinements to meet the quality requirements of the Pharmacopoeia

Method used

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Effect test

Embodiment 1

[0048] In the present embodiment, the preparation of nitration reaction, esterification reaction, mesylation reaction, reduction reaction and hydrolysis reaction in the preparation process of olsalazine sodium is related to "Improvement of Osalazine Synthesis Process" (Chen Xiaoquan, Zhai Hu, China Pharmacy, 2008, 19(16): 1222-1223), the steps described are the same and will not be repeated here.

[0049] Wherein, the step of diazotization coupling reaction is as follows:

[0050] (1) Dissolving 3-amino-6-methanesulfonyloxy-methyl benzoate in hydrochloric acid with a mass fraction of 10%, fully dissolved at room temperature after adding a catalyst;

[0051] (2) adding sodium nitrite and ice-water mixture to react to obtain a diazonium salt solution; in the ice-water mixture, the mass ratio of ice to water is 0.1:1; the mass fraction of sodium nitrite is 20%, and the reaction is 2h;

[0052] (3) step (2) repeats 2 times, the time of adding sodium nitrite and ice-water mixture ...

Embodiment 2

[0055] In the present embodiment, the preparation of nitration reaction, esterification reaction, mesylation reaction, reduction reaction and hydrolysis reaction in the preparation process of olsalazine sodium is related to "Improvement of Osalazine Synthesis Process" (Chen Xiaoquan, Zhai Hu, China Pharmacy, 2008, 19(16): 1222-1223), the steps described are the same and will not be repeated here.

[0056] Wherein, the step of diazotization coupling reaction is as follows:

[0057] (1) 3-amino-6-methanesulfonyloxy-benzoic acid methyl ester is dissolved in hydrochloric acid with a mass fraction of 25%, fully dissolved at room temperature after adding a catalyst;

[0058] (2) Add sodium nitrite and ice-water mixture to react to obtain a diazonium salt solution; in the ice-water mixture, the mass ratio of ice to water is 15:1; the mass fraction of sodium nitrite is 45%, and the reaction is 0.3h ;

[0059] (3) Add methyl salicylate and potassium hydroxide, adjust the pH to 10, fu...

Embodiment 3

[0061] In the present embodiment, the preparation of nitration reaction, esterification reaction, mesylation reaction, reduction reaction and hydrolysis reaction in the preparation process of olsalazine sodium is related to "Improvement of Osalazine Synthesis Process" (Chen Xiaoquan, Zhai Hu, China Pharmacy, 2008, 19(16): 1222-1223), the steps described are the same and will not be repeated here.

[0062] Wherein, the step of diazotization coupling reaction is as follows:

[0063] (1) 3-amino-6-methanesulfonyloxy-benzoic acid methyl ester is dissolved in hydrochloric acid with a mass fraction of 18%, fully dissolved at room temperature after adding a catalyst;

[0064] (2) Add sodium nitrite and ice-water mixture to react to obtain a diazonium salt solution; in the ice-water mixture, the mass ratio of ice to water is 7:1; the mass fraction of sodium nitrite is 32%, and the reaction is 1.2h ;

[0065] (3) step (2) repeats 3 times, the time of adding sodium nitrite and ice-wat...

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Abstract

The invention relates to the field of preparation of chemical medicines and particularly relates to Olsalazine sodium and a preparation method thereof. By adopting a method of adding an ice-water mixture, the problem that a side reaction is caused due to the adding rate of sodium nitrite is solved; by improving a diazotization coupling reaction method, the preparation method is simple in steps, low in toxicity and less in impurities in a product, the whole yield is greatly improved to 80% or higher, the quality of the product is ensured, and the effect is obvious; meanwhile, the percent of pass of primary refining of a finished product is improved, and the industrial cost is lowered. Therefore, the preparation method is beneficial for large-scale industrial production and promotion.

Description

technical field [0001] The invention relates to the field of chemical medicine preparation, in particular to olsalazine sodium and a preparation method thereof. Background technique [0002] Olsalazine sodium (Olsalazinesodium), namely 5,5'-azodisalicylate sodium, also known as olsalazide and diportan, is a drug developed by the Swiss PharmaciAB company and was first listed in Denmark in 1989. Olsalazine is split into two molecules of 5-aminosalicylic acid under the action of colonic bacteria and acts on the inflammatory mucosa of the colon, inhibits the synthesis of prostaglandins, inhibits the formation of inflammatory mediator leukotrienes, reduces the permeability of the intestinal wall cell membrane, and relieves intestinal inflammation. Mucous membrane edema, so it has anti-inflammatory, increase immunity, reduce the production of inflammatory mediators and so on. It is clinically used for the long-term maintenance treatment of acute and chronic ulcerative colitis, Cr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C245/08
CPCC07C245/08
Inventor 谢应波张庆张华徐肖冰罗桂云张维燕
Owner 上海泰坦科技股份有限公司
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