Synthesis process of rifaximin-D6

Abstract

The invention provides a synthesis process of rifaximine-D6, which comprises the following steps: 1) by using compounds I2-amino-4-methylpyridine and D2O as raw materials, reacting in the presence of5wt% palladium on carbon and under the protection of nitrogen to obtain a deuterated intermediate, i.e., a compound II 4-methyl-2-aminopyridine-D6; step 2), dissolving rifamycin S and the deuterated intermediate compound II 4-methyl-2-aminopyridine-D6 prepared in the step 1) into dichloromethane; under the protection of nitrogen, stirring at room temperature, dropwise adding a dichloromethane solution dissolved with elemental iodine, reacting at room temperature overnight for 18 hours, dropwise adding an L-ascorbic acid aqueous solution, stirring, and after the reaction is completed, washing and purifying to obtain the product rifaximin-D6. The synthesis method has the following technical effects that the synthesis method of the intermediate II of rifaximin-D6 is simple and convenient, andraw materials are easy to obtain; the steps for synthesizing rifaximin-D6 are simple and short, and the operation is easy.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, in particular to a synthesis process of rifaximin-D6. Background technique [0002] Rifaximin, a rifamycin derivative, is the first non-aminoglycoside enteric antibiotic. This product has a strong effect and a broad antibacterial spectrum. This product is effective against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus faecalis among Gram-positive aerobic bacteria; against Salmonella, Escherichia coli, Shigella, Yersinia enterocolitica, Cocci; Bacteroides among Gram-negative anaerobic bacteria are highly active. [0003] Rifaximin-D6 is stable isotope-labeled rifaximin. This compound can be used to study the toxicology and pharmacology of rifaximin. There is no report on the synthesis method of rifaximin-D6 at present. [0004] The structural formula of rifaximin-D6 is as follows: [0005] [0006] The synthetic method of existing rifaximin is as follows: ...

AI Technical Summary

Problems solved by technology

[0009] 1) No 4-methyl-2-aminopyridine-D6 is commercially available;

[0010] 2) The synthesis route of 4-methyl-2-aminopyridine-D6 is complex and has no synthetic significance

[0011] 3) Literature General method of obtaining deuterium-labeled heterocyclic compounds using neutral D 2 O with heterogeneous Pd / C reported the hydrogen-deuterium exchange of 4-methyl-2-aminopyridine-D6, but it needs to react at high temperature under hydrogen atmosphere, which is not safe enough

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