Process for producing pidotimod

Abstract

The invention discloses a process for producing pidotimod and belongs to the technical field of medicines. A pidotimod crude product is prepared by a one-pot method which mainly comprises the following steps: (1) in the presence of a condensing agent as a catalyst, carrying out condensation reaction on L-pyroglutamic acid and L-4-thiazolidine formate to produce pidotimod ester and after the reaction is completed, filtering solid to obtain a mother liquid; and (2) adding an appropriate amount of acid into the mother liquid for hydrolyzing pidotimod ester, after the reaction is completed, separating liquid, retaining an aqueous phase, precipitating solids in an ice bath and filtering to obtain pidotimod. The yield is greatly increased, the process is simple, no special device is needed and pidotimod is suitable for large-scale production. According to the preparation process of pidotimod, by preferably selecting the process parameters, the yield and purity are greatly improved. Compared with the prior art, the yield of the pharmaceutical-grade pidotimod pure product is increased by 10-20%.

Description

technical field [0001] The invention relates to a drug synthesis method, in particular to a production process of an immune function promoting agent pidotimod. Background technique [0002] Pidotimod, developed by the Italian company Poli industria chimica S.P.A in the 1980s, was approved for clinical use in 1993. It is a synthetic immune booster with a structure similar to dipeptide. Named (4R)-3-[[(2S)-5-oxo-2-pyrrolidinyl]carbonyl]-4-thiazolidinecarboxylic acid; has anti-toxicity, anti-irritation, anti-infection, anti-oxidation , anti-aging and other characteristics, can not only promote non-specific immune response, but also promote specific immune response; it is mainly used for the prevention and treatment of children's recurrent respiratory tract infection, urinary system infection, allergic rhinitis and asthma, and the treatment and prevention of acute chronic bronchitis attack, upper respiratory tract infection, and can also be used for a variety of viral infection...

AI Technical Summary

Problems solved by technology

[0005] (2) Using L-pyroglutamyl chloride and L-thiazolidine-4-carboxylic acid as raw materials, under the condition of acid bondage, amidation occurs to prepare pidotimod; when preparing acyl chloride, sulfur oxychloride, Phosphorus pentachloride or oxalyl chloride, etc., but thionyl chloride, phosphorus pentachloride, and oxalyl chloride are all toxic and corrosive, and can seriously irritate the eyes, skin and respiratory tract. The equipment used in production is severely corroded and the pollution problem is serious , the environmental problems are prominent, and their processes as chlorination reagents also have problems such as low product yield and purity

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