Preparation method of Ethanamizuril bulk drug

A technology of samizuril and raw materials, which is applied in the field of preparation of samizuril raw materials, can solve the problems of samizuril with many impurities, unfavorable samizuril application, and difficult purification, and achieve mild hydrolysis conditions, The effect of good industrial application value

Active Publication Date: 2021-03-09
HUBEI ZHONGMU ANDA PHARMACEUTICAL CO LTD +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] However, there are many impurities in the samizuril obtained by the above synthesis process route, and the purification is difficult, which is unfavorable for the application of samizuril in anticoccidial veterinary medicine

Method used

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  • Preparation method of Ethanamizuril bulk drug
  • Preparation method of Ethanamizuril bulk drug
  • Preparation method of Ethanamizuril bulk drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The present embodiment provides a kind of preparation method of samizuril crude drug, and its synthetic route is as follows figure 2 As shown, it specifically includes the following steps:

[0041] Synthesis of compound I:

[0042] At room temperature, in a 500mL round bottom flask, add solvent DMF (250mL), potassium carbonate (64g), paracetamol (61g, 0.40mol), after stirring for one hour, add 2-fluoro-5-nitrotoluene (62g, 0.36mol), heated to 140°C in an oil bath, stirred and reacted for 5h, removed the oil bath, stirred to cool down, added water (500mL), a large amount of light yellow solid precipitated, stirred for ten minutes, and suction filtered to obtain a solid product, water After washing and drying at 80°C, compound I was obtained, 103 g of light yellow powder, with a yield of 99.5%.

[0043] Recrystallized to obtain colorless needle crystals, melting point: 164.2-164.6°C. 1 H NMR (400MHz, DMSO-d 6 )δ10.06(s,1H),8.20(d,J=2.8Hz,1H),8.02(dd,J=9.1,2.9Hz,1H),7...

Embodiment 2

[0059] The present embodiment provides a kind of preparation method of samizuril crude drug, specifically comprises the following steps:

[0060] Synthesis of compound I:

[0061] At room temperature, in a 500mL round bottom flask, add the solvent DMAC (250mL), sodium carbonate (49g), paracetamol (59g, 0.39mol), after stirring for one hour, add 2-fluoro-5-nitrotoluene (62g, 0.36mol), heated to 140°C in an oil bath, stirred and reacted for 5h, removed the oil bath, stirred to cool down, added water (500mL), a large amount of light yellow solid precipitated, stirred for ten minutes, and suction filtered to obtain a solid product, water After washing and drying at 80°C, compound I was obtained, 102 g of light yellow powder, with a yield of 99.0%.

[0062] Synthesis of compound II:

[0063] In the 1000mL round bottom flask, add anhydrous methanol (500mL), ferric chloride (0.5g), gac (5g), sodium hydroxide (0.5g), compound I (100g, 0.35mol), in the oil bath, heat to Reflux, unde...

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Abstract

The invention provides a preparation method of a Ethanamizuril bulk drug, which comprises the following steps: reacting acetaminophen and 2-fluoro-5-nitrotoluene as initial raw materials to obtain a compound II, and carrying out diazotization coupling reaction to obtain a compound IV, wherein the conjugate adopted in the diazotization coupling reaction is a compound III. According to the preparation method of the Ethanamizuril bulk drug, malonic acid monoester monoamide formate is used as a conjugate, acetaminophen and 2-fluoro-5-nitrotoluene are used as initial raw materials, construction ofa triazine ring can be realized more efficiently and mildly, and the obtained target product samipril is higher in yield and purity.

Description

technical field [0001] The present invention relates to the technical field of organic synthesis, more specifically, to a preparation method of samizuril crude drug. Background technique [0002] Ethanamizruil, chemical name N-[4-[4-(4,5-dioxo-4,5-dihydro-1,2,4-triazine ring-(3H)-yl -2-Methylphenoxy)phenylacetamide is a triazine anticoccidial drug with a new chemical structure independently developed by the Shanghai Veterinary Research Institute of the Chinese Academy of Agricultural Sciences. No toxic side effects, good safety. There is no cross-resistance with existing anticoccidial drugs such as diclazuril and toltrazuril, and the anti-coccidial effect is more obvious, without oocysts and lesions. It is a good substitute for diclazuril and toltrazuril Taste. As a national first-class new veterinary drug, its successful industrialization application has far-reaching significance for poultry farming in my country, especially for the prevention and control of chicken cocc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D253/075
CPCC07D253/075
Inventor 张正海徐金雷蔡健麻红利梁景乐王峥
Owner HUBEI ZHONGMU ANDA PHARMACEUTICAL CO LTD
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