Process for synthesizing D-alpha-(6-methyl-4-hydroxyl nicotinamide base)p-hydroxyphenylacetic acid

Abstract

The invention relates to a method for synthesizing an intermediate of cephalosporins antibiotics cefpiramide, D-alpha-(6-methyl-4-hydroxy nicotinamido)-p-hydroxyphenyl acetic acid. The method comprises the steps of: reacting carboxyl group protected D-p-hydroxyphenyl glycine and anhydride or acyl chloride of 4-hydroxy-6-methylnicotinic acid to obtain acylated product, and hydrolyzing to remove the protecting group to obtain the target product D-alpha-(6-methyl-4-hydroxy nicotinamido)-p-hydroxyphenyl acetic acid. The method has the advantages of easy and feasible operation, and applicability to large scale production.

Description

Synthesis of D-α-(6-methyl-4-hydroxynicotinamide) p-hydroxyphenylacetic acid technical field The invention relates to a synthesis method of D-α-(6-methyl-4-hydroxynicotinamide) p-hydroxyphenylacetic acid, an acid intermediate at the 7-position of cefpiramide, a cephalosporin antibiotic, and belongs to the technical field of synthesis of pharmaceutical intermediates . Background technique The chemical name of cefpiramide (cefpiramide) is (6R, 7R)-7-[(R)-2-(4-hydroxy-6-methyl-3-pyridinecarbonylamino)-2-(p-hydroxyphenyl)acetyl Amino]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4,2,0] Oct-2-ene-2-carboxylic acid. Its structural formula is: Cefpiramide is a third-generation cephalosporin antibiotic jointly developed by Sumitomo Pharmaceutical Co., Ltd. and Yamanouchi Pharmaceutical Co., Ltd. It was first listed in Japan in 1985 and has been included in the American, Japanese, British and European Pharmacopoeias. It is characterized by broad anti...

AI Technical Summary

Problems solved by technology

The structure of the compound is complex, the synthetic route is long, and the reaction conditions are harsh, thereby restricting the production of cefpiramide bulk drug

Patent JP54-030197 introduces a synthetic method of D-α-(6-methyl-4-hydroxynicotinamide) p-hydroxyphenylacetic acid (I) in the form of a reference example, but because its intermediates need to pass through Dry hydrogen chloride gas is made into hydrochloride, which requires high equipment and operation, which is not conducive to large-scale industrial production

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