A kind of preparation method of mitiglinide calcium

Abstract

The invention provides a novel preparation method for Mitiglinide calcium hydrate. The method comprises the following steps: adopting cis-hexahydroisoindole as a raw material, conducting acylation reaction, hydrocarbonylation reaction, hydrolysis reaction, and salt forming reaction on the raw material, and obtaining the Mitiglinide calcium hydrate; a one-port process method is adopted for conducting the hydrocarbonylation reaction and the hydrolysis reaction, and the product purity can reach over 99.8%, and the yield can reach over 36%. The preparation method for Mitiglinide calcium hydrate has the advantages of the easy-to-get raw material, mild reaction condition, simple and practicable operation, and relatively high yield, therefore, the method has relatively higher industrial production value, and industrialization has been realized at present.

Description

technical field

[0001] The invention relates to the field of medicine, in particular, the invention relates to a preparation method of mitiglinide calcium. Background technique

[0002] Bis[(2s)-2-benzyl-3-(cis-hexahydroisoindole-2-carbonyl)propanoic acid] monocalcium dihydrate (mitiglinide calcium), molecular formula C 38 h 48 CaN 2 o 6 2H 2 O, the English name is MitiglinideCalciumHydrate, and the structural formula (I) is as follows:

[0003]

[0004] Miglinide Calcium was synthesized by Japan Tachibana Pharmaceutical Co., Ltd. and launched in Japan in April 2004. It is used for type Ⅱ diabetic patients whose hyperglycemia cannot be effectively controlled by diet and exercise therapy. Miglinide calcium is the third meglitide drug after repaglinide and nateglinide, which is a derivative of phenylalanine. Miglinide calcium closes the ATP-dependent K channel on the pancreatic β-cell membrane, causing Ca influx, increasing the intracellular Ca concentration and degra...

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