Repaglinide synthesis process

Abstract

This invention discloses a process for synthesizing repaglinide by using 4-carboxymethyl-3-ethoxybenzoate as raw material to produce acyl chloride. Compared to other process, this invention is characterized of high efficiency, low toxicity, easy obtained and cheap raw material, simple operation, and high yield with 80.9% total yield rate in two-step reaction, which makes it a good repaglinide systhesis process with good industrialization future.

Description

technical field [0001] The invention relates to the field of organic synthesis of medicines, in particular to a process for synthesizing repaglinide Background technique [0002] The chemical name of repaglinide is S(+)-2-ethoxy-4-[N-{1-(2-piperidinylphenyl)-3-methyl-1-butyl}amine Cylcarbonylmethyl]benzoic acid, a new type of oral hypoglycemic drug belonging to the methylbenzylamine benzoic acid (CBMA) family, can promote insulin secretion. It is different from the binding site of β cells and sulfonylureas, and has With the characteristics of fast absorption, fast onset and short action time, it can simulate physiological insulin secretion in patients with type II diabetes, effectively control postprandial hyperglycemia, has a high protein binding rate, and will not accumulate in tissues. Good safety, and synergistic effect with biguanides. It can be used alone as a first-line antidiabetic drug, and can also be used in combination with other hypoglycemic drugs to increase ...

AI Technical Summary

Problems solved by technology

In the process mentioned in the patent, N,N'-dicyclohexylcarbodiimide is used to synthesize, and the product needs to be recrystallized multiple times to remove the by-product N,N'-dicyclohexylurea, which increases the production cost; Utilize the product yield that carbonyldiimidazole catalyzes synthesis to obtain low, only have 50~55%, and carbonyldiimidazole is relatively more expensive; And utilize triphenylphosphine, triethylamine, carbon tetrachloride to synthesize, this method Although the yield has increased, the purity of the product can only be achieved by column chromatography

[0006] Subsequently, a new process for the synthesis of repaglinide reported in US2005 / 0107614 is obtained by condensation of compound 2 and compound 3 in the presence of tert-butylacetyl chloride and alkali. Although the process is simple to operate and the product is easy to purify, However, the reaction time of the process is long, and the yield is not high, only about 73%, and the tert-butylacetyl chloride used is relatively expensive

[0007] In these two patents, although the yield of the process mentioned in US5,312,924 is relatively high, the product is difficult to purify, and it is difficult to realize the industrial production of repaglinide

And patent US2005 / 0107614 provides a kind of technology that product is easy to purify, but reaction time is too long, and yield is not very high, also makes its application prospect limited

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