Preparation method of high-purity rifapentine

Abstract

The invention provides a preparation method of high-purity rifapentine, which is characterized by comprising the following steps: 1. carrying out a cyclization reaction on rifamycin S acid, acid and dimethyloltert-butylamine in an N, N-dimethylformamide solvent; 2, pouring the reaction solution into acid water, standing, and filtering to obtain a rifaxizine filter cake; 3, adding urea, n-butyl alcohol, Vc and sodium carbonate into the rifaxizine filter cake for a ring-opening reaction; 4, after the reaction is completed, increasing the purity to 1-amino-4-cyclopentylpiperazine for a condensation reaction until the reaction is completed so as to obtain a rifapentine reaction solution; and step 5, dropwise adding acid water into the rifapentine reaction solution, stirring, stopping heating after crystallization, lowering the rotating speed after turning red, cooling after dropwise adding is finished, filtering to obtain the filter cake, and carrying out secondary recrystallization on thefilter cake. According to the preparation method of the high-purity rifapentine, provided by the invention, the maximum single impurity of the rifapentine can be controlled within 0.1%, and the residual n-butyl alcohol and the residual ethanol can be controlled within 0.5%.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a preparation method of high-purity rifapentine. Background technique [0002] Rifapentine is an anti-tuberculosis drug produced through a synthetic reaction based on the raw material of rifamycin S acid, and its chemical structural formula is as follows: [0003] [0004] Rifapentine is a semi-synthetic broad-spectrum fungicide, which has strong antibacterial activity against Mycobacterium tuberculosis in vitro, with a minimum inhibitory concentration (MIC) of 0.12-0.25 mg / L, which is 2-10 times stronger than rifampicin; The anti-tuberculosis infection in mice is also better than rifampicin. Bacillus leprae and other mycobacteria such as Mycobacterium kansasii and Mycobacterium xenopus are also sensitive to this product, but Mycobacterium avium is resistant. In addition, this product has high antibacterial activity against most Gram-positive cocci, and its MIC<0.025mg / L...

AI Technical Summary

Problems solved by technology

[0005] The mechanism of action of rifapentine is the same as that of rifampicin. It binds firmly to the subunit of DNA-dependent RNA polymerase, inhibits the synthesis of bacterial RNA, prevents the enzyme from connecting with DNA, thereby blocking the RNA transcription process and making DNA and protein The synthesis is stopped, but in the prior art, the purity of rifapentine is not enough, and the use effect is not satisfactory

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