Method for compounding 2,6-dichloropurine nucleoside by using inosine as raw material

Abstract

The invention discloses a method for compounding 2,6-dichloropurine nucleoside by using inosine as a raw material. The method is characterized by using cheap inosine as the raw material; obtaining 6-chlorine triacetyl purine nucleoside through acetylation and chlorination reactions; then enabling the 6-chlorine triacetyl purine nucleoside to react with trifluoromethanesulfonic acid; introducing nitro in at a second site; finally completing two reactions of acetyl removing and nitro chlorination in an ethanol solution which is saturated by a hydrogen chloride gas, obtaining the 2,6-dichloropurine nucleoside, wherein the total yield is 63 percent. According to the method for compounding the 2,6-dichloropurine nucleoside by using the inosine as the raw material, disclosed by the invention, the raw materials are cheap and are easily obtained, a reagent of which the price is expensive and poisonous and harmful heavy metal catalysts are prevented from being used, and the yield is not obviously reduced when the reaction scale is enlarged to 200 g; a new compounding way is provided for compounding of the 2,6-dichloropurine nucleoside, and a potential application prospect is obtained.

Description

technical field [0001] The invention relates to a method for synthesizing 2,6-dichloropurine nucleoside, in particular to a method for synthesizing 2,6-dichloropurine nucleoside with inosine as a raw material. Background technique [0002] 2,6-Dichloropurine nucleoside has significant anti-tumor and anti-viral drug activity, especially has a good curative effect on the treatment of infections caused by mycoplasma. At the same time, it is also a widely used pharmaceutical intermediate, used to synthesize a series of nucleoside substances with good pharmacological activity, such as anticancer drug 2-chloroadenosine, adenosine A3 receptor agonist, etc. Therefore, the synthesis of 2,6-dichloropurine nucleoside is of great significance. [0003] At present, the synthesis methods of 2,6-dichloropurine nucleoside reported in the literature mainly include: 1. Condensation method. Such as Schaefe et al. [4] The mercury salt of 2,6-dichloropurine is condensed with 1-chloro-2,3,5-tr...

AI Technical Summary

Problems solved by technology

The disadvantages of these methods are: (1) the price of 2,6-dichloropurine is higher, and there are many preparation steps; (2) heavy metal catalyst mercury salt or SnCl 4 High toxicity, easy residue, large environmental pollution

The former requires the use of an explosive diazotization step, while the latter has many synthesis steps and a higher price

[0004] Therefore, the reported method for synthesizing 2,6-dichloropurine nucleoside (the market price is about 20,000 yuan / Kg) has high raw material cost and complex synthesis process, which limits the expansion of production scale.

Images