A kind of preparation method of trimethoprim

Abstract

The invention discloses a nequinate preparation method, and relates to a broad-spectrum coccidiostat preparation method which sequentially includes the steps: taking 4-butyl-3-benzyloxy aniline as raw materials; sequentially performing substitution reaction on the 4-butyl-3-benzyloxy aniline and 2-cyano-3-methoxy ethyl acrylate; performing ring closing reaction on the 4-butyl-3-benzyloxy aniline and the 2-cyano-3-methoxy ethyl acrylate; performing hydrolysis and esterification reaction on the 4-butyl-3-benzyloxy aniline and the 2-cyano-3-methoxy ethyl acrylate under the acid condition to prepare nequinate. The invention provides a new synthesis route, raw materials such as methoxy methylene are not used, reactions are mild in condition, simple in process and conventional to operate, and extreme reaction conditions are effectively avoided.

Description

technical field [0001] The invention relates to a preparation method of anticoccidial medicine, in particular to a method for preparing trimethoprim. Background technique [0002] In the raising process of modern animal husbandry, livestock and poultry are easily infected by coccidiosis and are attacked by coccidiosis. In recent years, more and more attention has been paid to anti-coccidia drugs, and anti-coccidia veterinary drugs are also widely used. It is used in animal husbandry, and quinoline anticoccidiostats are an important veterinary drug raw material. Since there are mainly quinoline rings in its molecular structure, it is possible to form different types of anticoccidial raw materials by adding different substituents. Among them, there are mainly butyl hydroxyquinoline (Byqyunilate butyl quinoline), ethoquinoline (Decoquinate decoquinate, decanoquinate, decoquinate), trimethoprazil (Methylbenzoquat methylbenzylquinoline, methylbenzene quinoate, benzyl quinoate) ...

AI Technical Summary

Problems solved by technology

[0003] At present, in the domestic market, trimethoprim mainly depends on imports. Due to the high price, the market share is not high. If localization can be realized and the cost of use can be effectively reduced, it will definitely promote the development of this type of veterinary drug and animal husbandry in my country. develop

[0004] The manufacturer of this type of coccidiostat produced on a large scale is mainly U.S. Eli Lilly and Company in the world at present, and the main preparation method of trimethoprim is to use methoxymethylene malonate as a condensation agent, and then at high temperature Conditions (greater than 200°C) for ring closure to obtain products (Italian patent IT1320189 and world patent WO9911602), because the domestic supply of dimethylmethoxymethylenemalonate is not large, and the price is relatively expensive, and there are relatively large irritation, which severely limits the mass production of this method

[0005] After consulting a large number of domestic and foreign related documents and patents, we proposed a synthetic route with independent intellectual property rights to synthesize trimethoprim, using domestic cheap and easy-to-obtain ethyl 2-cyano-3-methoxyacrylate as Condensing agent, and the ring-closing solvent has been improved. Although there is an extra step of hydrolysis and esterification, the yield of each step is high, and they are all conventional operations, with good production prospects.

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