Production method of iguratimod intermediate

Abstract

The invention discloses a production method of an iguratimod intermediate, which comprises the following steps: S1, by using alpha-amino-2-methoxy-4-methanesulfonylamino-5-phenoxy acetophenone hydrochloride as a starting raw material, selecting a 100L reaction kettle, and adding 27kg of acetone and 1kg of sodium carbonate into the reaction kettle, wherein pivaloyl chloride is taken as an acylatingagent. The preparation method is simple in process and low in production cost, that is, sodium carbonate is added into the reaction raw material to generate impurities in the reaction process of pivaloyl chloride and sodium formate to generate sodium salt, so that the impurities cannot continuously react with alpha-amino-2-methoxy-4-methanesulfonylamino-5-phenoxy acetophenone hydrochloride, the generation of reaction impurities is reduced, the purity of the product is improved, the product is not refined to obtain a target product, and the yield is 85-95%.

Description

Technical field[0001]The present invention relates to the technical field of medicine, in particular to a production method of Iramod intermediate.Background technique[0002]Iramod is a new type of disease-relieving medicine for the treatment of rheumatoid arthritis and osteoarthritis jointly developed by Japan's Toyama Yu Eisai Pharmaceutical Company. Compared with other drugs, its characteristics are rapid and effective, and its efficacy is equivalent to that of highly effective antirheumatic drugs, but its toxicity is lower.[0003]N-(7-(Methylsulfonamide O)-4-oxo-6-phenoxy-4H-benzopyran-3-yl)carboxamide; N-[3-(carboxamido)-4 -Oxy-6-phenoxy-4H-1-benzopyran-7-yl]methanesulfonamide is a key intermediate in the synthesis of ilamod, due to the small amount of water contained in the acetone used in the production process Pivaloyl chloride is decomposed, and impurities are generated in the reaction process. The raw materials continue to react to form impurities that are not easy to remove...

AI Technical Summary

Problems solved by technology

[0003] N-(7-(methylsulfonamide O)-4-oxo-6-phenoxy-4H-benzopyran-3-yl)formamide; N-[3-(formamido)-4 -Oxy-6-phenoxy-4H-1-benzopyran-7-yl]methanesulfonamide is a key intermediate in the synthesis of drug iguratimod, due to the small amount of water contained in the acetone used in the production process The pivaloyl chloride is decomposed, and impurities are produced during the reaction process. The raw materials continue to react to form impurities that are not easy to remove, and the reaction cannot be carried out completely, with a yield of 30-40%. The product must be refined, which puts pressure on cost and environmental protection requirements. It is very large and causes huge waste. Therefore, we propose a production method of Alamod intermediate to solve the above problems