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Preparation method of anticoccidial drug Diclazuril

A technology of diclazuril and anticoccidiostats, applied in the field of drug synthesis, to achieve the effect of increasing yield

Active Publication Date: 2018-03-02
CHANGZHOU YABANG QH PHARMACHEM +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The object of the present invention is to provide a preparation method of the anticoccidial drug diclazuril, the method is simple in process, easy to operate, solves the odor generation of decarboxylation reaction in the production process, is beneficial to environmental protection, and is suitable for industrial production

Method used

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  • Preparation method of anticoccidial drug Diclazuril

Examples

Experimental program
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Effect test

preparation example Construction

[0021] Preparation of 3,4,5-trichloronitrobenzene

[0022] Put 62.5 mL of concentrated sulfuric acid into a 250 mL four-necked flask, and add 11.5 g of sodium nitrite under stirring. The temperature was raised to 70°C and stirred for 10 minutes, then the temperature was reduced to 55°C, 31.2g of 2,6-dichloro-4-nitroaniline was slowly added, and the temperature was lowered to 5°C after 20 minutes of holding. The diazonium solution prepared by adding 40 mL of acetic acid and keeping the temperature for 30 minutes.

[0023] Add 125 mL of 36.5% hydrochloric acid and 15 g of cuprous chloride to another 250 mL four-necked flask. After stirring for 15 minutes, the above diazonium liquid is slowly added dropwise. The temperature during the dropping process is controlled below 25°C. After the dripping, the temperature was raised to 70°C and kept for 1 hour. After the incubation, the temperature is lowered to room temperature and filtered, and washed with 1% lye. The brown crystals obtai...

Embodiment 1

[0025] Preparation of 2,6-Dichloro-α-(4-chlorophenyl)-4-nitrobenzeneacetonitrile

[0026] Into a 500 mL four-necked flask, 170 mL of 2-butanone, 55 g of 3,4,5-trichloronitrobenzene, and 40.5 g of p-chlorobenzene acetonitrile were placed, and the temperature was raised to 50°C. 50% sodium hydroxide solution was added dropwise, and the reaction was kept for 2h after the dropping. After the incubation, the temperature was lowered to 25°C and hydrochloric acid was added dropwise to adjust pH=2. After adding 70 mL of water, the temperature was raised to 50° C. to separate layers. The water layer was removed, and the organic layer was distilled under reduced pressure to collect 2-butanone for recycling. Methanol was added and the temperature was reduced to 20° C., and 74.7 g of light yellow condensate powder was obtained by filtration. The yield was 90%, and the content was 99.59% (HPLC).

[0027] Preparation of 2,6-Dichloro-α-(4-chlorophenyl)-4-aminobenzeneacetonitrile

[0028] Into a...

Embodiment 2

[0032] Preparation of 2,6-Dichloro-α-(4-chlorophenyl)-4-nitrobenzeneacetonitrile

[0033] Into a 500 mL four-necked flask, 200 mL of 2-butanone, 55 g of 3,4,5-trichloronitrobenzene, and 42.4 g of p-chlorobenzene acetonitrile were placed, and the temperature was raised to 50°C. 30% sodium hydroxide solution was added dropwise, and the reaction was kept for 3 hours after the dropping. After the incubation, the temperature was lowered to 30°C and hydrochloric acid was added dropwise to adjust the pH=1. After adding 55 mL of water, the temperature was raised to 55°C to separate layers. The water layer was removed, and the organic layer was distilled under reduced pressure to collect 2-butanone for recycling. The temperature was lowered to 20°C by adding methanol, and 73.04 g of light yellow condensate powder was obtained by filtration, the yield was 88%, and the content was 99.3% (HPLC).

[0034] Preparation of 2,6-Dichloro-α-(4-chlorophenyl)-4-aminobenzeneacetonitrile

[0035] Into ...

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Abstract

The invention discloses a preparation method of an anticoccidial drug Diclazuril. The method takes 3,4,5-trichloronitrobenzene as a raw material and the 3,4,5-trichloronitrobenzene and 4-chlorobenzylcyanide are subjected to condensation reaction to generate 2,6-dichloro-alpha-(4-chlorobenzyl)-4-nitrophenylacetonitrile; enabling a condensate and hydrazine hydrate to be subjected to reduction to generate 2,6-dichloro-alpha-(4-chlorobenzyl)-4-aminophenylacetonitrile, enabling a reduzate and malonyl ethyl dicarbamate to be subjected to diazo, coupling, cyclization, hydrolysis and decarboxylationone-pot reaction to generate the Diclazuril. The method disclosed by the invention has a simple technology and is easy to operate; the environment protection problem caused by the fact that the odor of thioglycolic acid is great in a decarboxylation process of the Diclazuril is solved; meanwhile, the yield is improved and the total yield of the Diclazuril synthesized by taking 2,6-dichloro p-nitroaniline as the raw material is 43.8 percent, so that the preparation method is suitable for industrial production.

Description

Technical field [0001] The invention relates to a method for preparing an anticoccidial drug diclazuril, which belongs to the technical field of drug synthesis. Background technique [0002] Diclazuril (Diclazuril), also known as chloroazine benzene acetonitrile, chemical name: 2,6-dichloro-α-(4-chlorophenyl)-4-(4,5-dihydro-3,5-dichloro Substitute-1,2,4-triazine-2(3H)-yl)benzeneacetonitrile, white or off-white powder, slightly soluble in DMF, tetrahydrofuran, insoluble in water or ethanol. Diclazuril is a non-ionic anticoccidial drug. It was first developed and put into the market in 1992 by Janssen of Belgium. It is a safe, efficient, broad-spectrum, and residue-free new anticoccidial drug. Its structural formula is as follows: [0003] [0004] At present, there are few reports on the synthesis method of diclazuril in China. The reported literature uses 2,6-dichloro-p-nitroaniline as raw material, diazotized, condensation, reduction, and then reacts with ethyl cyanoaceturethane...

Claims

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Application Information

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IPC IPC(8): C07D253/075
CPCC07D253/075
Inventor 张建峰郑爱华朱云兵刘永林潘如龙谢琪
Owner CHANGZHOU YABANG QH PHARMACHEM
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