Process for preparing indobufen

A technology based on indobufen and isoindoline, which is applied in the field of preparation of indobufen, can solve the problems of being unsuitable for industrial production, high toxicity, and difficulty in dissolving residues, so as to be beneficial to the health protection of employees, Low impurity content, the effect of environmental protection workers' health protection

Active Publication Date: 2019-03-19
HANGZHOU ZHONGMEI HUADONG PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The yield of this method is only 64%
At the same time, dioxane is a second-class solvent, which has technical difficulties such as high toxicity and difficulty in dissolving residues, and is also very unsuitable for industrial production.

Method used

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  • Process for preparing indobufen
  • Process for preparing indobufen
  • Process for preparing indobufen

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1, hydrogenation reaction and cyclization reaction

[0029] Add 85kg of 2-(4-nitrophenyl)butyric acid, 2.2kg of Pd / C catalyst, and 850L of acetic acid into the hydrogenation reactor, start stirring, and feed hydrogen to control the hydrogen pressure at 1.0Mpa and the reaction temperature at 25°C , carry out the hydrogenation reaction, keep the hydrogen pressure at 1.0Mpa, when the hydrogen is no longer consumed, stop the reaction, filter to obtain 2-(4-aminophenyl)butyric acid filtrate.

[0030] Put the 2-(4-aminophenyl)butyric acid filtrate into the reaction kettle, when the temperature rises to 40°C, slowly add 136 kg of phthalic anhydride, continue to heat up to 80°C, stir for 3 hours, and the cyclization reaction ends . Cool down to 25°C, centrifuge and dry to obtain 113.1 kg of 2-[4-(1,3-dioxo-2-isoindolinyl]phenylbutyric acid, yield 89.9%, mp 216~ 218°C.

Embodiment 2-5

[0031] Embodiment 2-5, hydrogenation reaction, cyclization reaction and comparative test

[0032] Following examples 2-5, all take 85 kilograms of 2-(4-nitrophenyl) butyric acid as starting reaction material. Except specifying, other materials, technique are identical with embodiment 1.

[0033]

[0034] In the above table, Example 5 wherein is the yield and purity after carrying out the industrial scale-up test according to the technique of prior art 2;

[0035] As can be seen from the above table, when the selection of materials and / or process conditions is outside the protection scope of the present application, the yield of intermediates is low, and the melting point is not within the standard, which indicates that more impurities may be produced .

Embodiment 6

[0036] Embodiment 6, zinc powder reduction reaction

[0037] 80 kilograms of 2-[4-(1,3-dioxo-2-isoindolinyl] phenylbutyric acid and 480L acetic acid prepared by the method of Example 1 were dropped into a reaction tank, and the stirring was started, and 64 kilograms of Put the zinc powder into the reaction tank, feed hydrogen chloride gas under normal pressure, and control the reaction temperature at 82°C. The reaction starts, the reaction time is 1 hour, and the reaction feed liquid is all clarified. Filter, wash the filter residue with acetic acid, combine the filtrate and washing liquid, and decompress Recover the solvent, pour the residual liquid into an appropriate amount of water, stir, adjust the pH to 5.5-6.5 with ammonia water, and centrifuge and dry to obtain 72.3 kg of indobufen crude product, with a yield of 94.7%, a purity of 98.0%, a simple impurity content of less than 1.2%, and mp 182- 183°C.

[0038] After the crude product of indobufen is refined with activa...

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Abstract

The invention discloses a method for preparing indobufen; by optimizing the processes such as using a carbon-supported noble metal as a catalyst in hydrogenation reduction, using a suitable organic acid solvent in zinc powder reduction and introducing hydrogen chloride gas, the preparation method of indobufen is simple to perform and high in yield; the whole preparation method is good in safety, environmentally friendly, good for protecting the health of workers and suitable for industrial use, and the purity of prepared indobufen is high.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and in particular relates to a preparation method of indobufen. Background technique [0002] Indobufen is an anti-platelet aggregation drug, it can selectively act on circulating platelets, block thrombus formation, inhibit the release of platelet factors and play an anti-platelet aggregation effect, this inhibition is reversible, does not change plasma parameters, and does not damage platelets function, and restore abnormal platelet function to normal. It can significantly improve the microcirculation parameters and walking distance of patients with peripheral vascular disease and intermittent claudication, and it has the same effect as aspirin plus dipyridamole in preventing obstruction after coronary artery bypass surgery and femoral artery bypass surgery; during hemodialysis, It can significantly reduce platelet deposits on the dialysis membrane, and this product can also preve...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/34
CPCC07D209/34
Inventor 曹东生韩涛周汉君余睿
Owner HANGZHOU ZHONGMEI HUADONG PHARMA
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