Posaconazole, composition, intermediate, preparation method and application thereof

Abstract

The invention relates to a compound as shown in the formula III, wherein R is selected from C1-C4 alkyl group, substituted or unsubstituted phenyl group and substituted or unsubstituted benzyl group, and is preferably selected from isopropyl group; and two Ar can be the same or different, respectively and separately selected from substituted or unsubstituted aryl group, and preferably selected from substituted or unsubstituted phenyl group, such as methoxyphenyl, etc. The compound is preferably in a solid form.

Description

technical field The invention relates to the technical field of medicine, in particular to posaconazole, a composition, an intermediate, a synthesis method thereof and an application in synthesizing posaconazole. Background technique Posaconazole (CAS Registry No. 171228-49-2; CAS Name: 2,5-anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4 -[[4-[4-[1-(1S,2S)-1-ethyl-2-hydroxypropyl]-1,5-dihydro-5-oxo-4H-1,2,4-tri Azol-4-yl]phenyl]-1-piperazinyl]phenoxy]methyl]-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitol ), for the prevention and treatment of invasive fungal infections, drug-resistant or ineffective invasive fungal infections with other drugs, the structure is as follows: One of the important intermediates for the preparation of posaconazole is a compound of formula IX, Wherein Q is substituted or unsubstituted benzenesulfonyl, p-toluenesulfonyl or p-chlorobenzenesulfonyl, etc. The synthesis of this intermediate is reported in the patent US5403937A (1), Its chara...

AI Technical Summary

Problems solved by technology

It is characterized in that R-4-phenyloxazolidinone is a chiral prosthetic group, and the prosthetic group is removed by hydrolysis with sodium hydroxide and hydrogen peroxide. Although this route avoids column chromatography separation to obtain the iodic acid intermediate (formula-7 ) and chiral prosthetic groups, but the preparation of compound formula-6 by iodo ring closure still needs to use excess iodine in one step, and faces the same problem as the above-mentioned patent

In addition, the step of removing prosthetic groups by hydrolysis with sodium hydroxide is dangerous in industrial production due to the use of hydrogen peroxide.

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