Improved method of preparation of trifluridine

Abstract

The invention relates to a method for preparing trifluridine (Viroptic). The method comprises the following main steps: by using uridine (a compound shown in a formula II) as a starting raw material,sequentially carrying out the steps such as esterification and halogenating reaction of hydroxyl, reduction reaction, trifluoromethylation reaction and protective group removal reaction so as to obtain a target. The method provided by the invention has the advantages that the use of expensive raw materials and the use of reagents with high toxicity and capability of polluting an environment are avoided and reaction conditions required in all steps are mild; therefore, the invention provides a preparation method of trifluridine with environmental protection property, security property and a commercial preparation value.

Description

technical field [0001] The invention relates to a method for preparing "Trifluridine, Viroptic". Background technique [0002] "Trifluridine" (its structure is shown in formula I) is a class of drugs used to prevent and treat viral infections (mainly applicable to the treatment of herpes simplex keratitis, conjunctivitis and other herpetic eye diseases, etc.). In recent years, as its new uses have been continuously developed, its demand has also continued to rise. [0003] [0004] There are mainly the following methods for the preparation of "Trifluridine" that have been reported so far: [0005] (1) Using 2'-deoxyuridine as raw material, the active hydroxyl group is protected by esterification, and then trifluoromethylation reagent is used as trifluoroacetic acid, and trifluoromethylation is realized by the action of xenon difluoride, and finally removed Acetyl groups gave the target product in less than 24% overall yield (Noritada Matsuo, J. Org. Chem., 1988, 53(19),...

AI Technical Summary

Problems solved by technology

[0006] The disadvantages of this method are: ① the price of 2'-deoxyuridine (raw material) used is relatively expensive, ② the xenon difluoride used is not only highly toxic, but also highly corrosive to water, resulting in high requirements for equipment, ③ the total yield is low

[0010] Although this method avoids the use of highly toxic trifluoromethylation reagents, the price of 5-trifluoromethyluracil and 2-deoxy-D-ribose is relatively expensive, the synthesis route is long, and the separation of isomers is difficult. insufficient

In addition, a large amount of Lewis acid (copper fluoride) needs to be used in the condensation step of the method, resulting in difficulties in post-processing and environmental pollution.

Images