Synthesis method of remdesivir intermediate

Abstract

The invention relates to the technical field of medical intermediates, in particular to a synthetic method of a remdesivir intermediate. The chemical name of the intermediate is (3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-di(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2-ol. The preparation method comprises the following steps: performing amino protection on pyrrolo[2,1-F][1,2,4]triazin-4-amine with a protecting agent; reacting with lithium diisopropylamide; then adding 2,3,5-tribenzyloxy-D-ribonic acid 1,4-lactone, and finally removing the protective group to obtain the remdesivir intermediate that is the (3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-di(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2-ol.

Description

technical field

[0001] The invention relates to the field of pharmaceutical intermediates, specifically a method for synthesizing a remdesivir intermediate. Background technique

[0002] Remdesivir is a drug under research by Gilead Chemical. Remdesivir is a nucleoside analog with antiviral activity, with an EC50 value of 74 nM against ARS-CoV and MERS-CoV in HAE cells and an EC50 value against murine hepatitis virus in delayed brain tumor cells is 30nM.

[0003] At present, there are roughly two routes for the synthesis of remdesivir at home and abroad, as follows:

[0004] (1) The route adopted by the original manufacturer Gilead’s patent WO2016069826A1 is: (3R,4R,5R)-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2- Alcohol is used as the starting material, and remdesivir is obtained through oxidation, addition, substitution, resolution, debenzylation, protection, substitution, and finally resolution.

[0005]

[0006] (2) "Nature" reported the second-gene...

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