Method for preparing bilastine

Abstract

The invention relates to a method for preparing bilastine. The method comprises the following steps: adding a compound I oxazolol to water, adding a phase transfer catalyst, p-toluenesulfonyl chlorideand sodium hydroxide, stirring and reacting all above substances, and performing filtration to obtain oxazolol sulfonate; adding the sulfonate to water, adding 2-(4-piperidinyl)-1-H-benzimidazole andthe phase transfer catalyst, adding sodium carbonate or potassium carbonate, heating the obtained suspension, performing a reaction for 3-5 h, filtering the obtained intermediate II, adding the intermediate II to a strong polar aprotic solvent, adding sodium hydroxide and the phase transfer catalyst, adding ethylene glycol monoethyl ether tosylate, stirring and reacting the obtained mixture at -20-60 DEG C, filtering the obtained reaction product, and washing the filtered reaction product with water to obtain an intermediate III; and adding the intermediate III to an aqueous solution of an organic acid, performing refluxing for 3-5 h, adding water, adding a strong alkali until saturation, refluxing the obtained solution for 3-5 h to generate a bilastine salt insoluble in the saturated alkaline solution, and performing extraction to obtain the bilastine. The method has the advantages of mild reaction conditions, simplicity in operation, greenness, environmental protection, high yield,and convenience in industrial production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to the preparation of Bilastine. Background technique [0002] Bilastine (Bilst for short), the chemical name is 2-[4-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzimidazol-2-yl}B base)-phenyl]2-methyl-propionic acid, cas number 202189-78-4,. Bilastine is an oral second-generation histamine H1 receptor antagonist developed by Spanish FAES Pharmaceutical Company. It was registered as a new drug in the European Union in 2009, and was first approved for marketing in the UK and Ireland in 2011, and then successively marketed in Italy, Japan, Canada and other countries. It is used for the treatment of seasonal allergic rhinitis and perennial allergic rhinitis. The dosage specification is 20mg / piece. Other approved indications include pruritus, eczema and hives. This product is safe, without the sedative effect and cardiotoxicity of commonly used antihistamines. The structural formula of bilastin...

AI Technical Summary

Problems solved by technology

[0009] Those skilled in the art know that DMF is expensive and not environmentally friendly, and the aftertreatment is cumbersome. NaH is flammable and explosive, and industrial operation is difficult. If the hydrolysis is complete, if the hydrolysis time is too long and the temperature is too high, impurities will be formed that are difficult to remove, resulting in a decrease in the quality of the drug and a decrease in the yield

Directly adjusting the acid or alkali solution after the reaction to be neutral will cause severe heat release, increase the amount of the entire solvent, and make the reaction difficult to operate

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