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,

Method used

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  • Preparation method of anticoccidial drug Diclazuril

Examples

Experimental program
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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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