Synthetic method of adenine and its derivatives

Abstract

The invention discloses a method for synthesizing adenine and derivatives thereof. The method comprises the steps: firstly, subjecting diethyl malonate and dimethyl dioxirane to an oxidation reaction, so as to obtain 2-hydroxyldiethyl malonate; then, carrying out an ammonolysis reaction with ammonia water, so as to obtain 2-hydroxyl malonamide; then, carrying out a cyclization reaction with trimethyl orthoformate, so as to obtain 5-hydroxyl pyrimid-4,6-(1H,5H)-dione; then, carrying out a chlorination reaction with phosgene, so as to obtain 4,5,6-trichloropyrimidine; then, carrying out a cyclization reaction with formamidine hydrochloride, so as to obtain 4-chloro-1H-pyrazol[3, 4-d]pyrimidine; finally, carrying out an ammoniation reaction with ammonia water or an amine compound in the presence of triethylamine, thereby obtaining the adenine and derivatives thereof. According to the method, the raw materials are moderately-priced and readily available, the reaction conditions are mild, the reaction process is safe, the requirements on production equipment are low, particularly, the environmental pollution is light, and the yield is relatively high, so that the method is applicable to industrial large-scale production.

Description

technical field [0001] The invention relates to the field of pharmaceutical biochemical industry, in particular to a synthesis method of adenine and its derivatives. Background technique [0002] Adenine, whose chemical name is 6-aminopurine, is a component of nucleic acid and is mainly used to participate in the synthesis of RNA and DNA in organisms. When white blood cells are deficient, it can promote white blood cell proliferation. Adenine has the function of phytokinin, and its tablet or injection can be used for granulocytopenia, etc., and can also be used for the preparation of biochemical reagents and purine derivatives and other drugs, and can also be used for blood storage. [0003] At present, the synthetic methods of adenine mainly include adenosine method, hypoxanthine method and diethyl malonate method. [0004] The disadvantage of the adenosine method is that the price of adenosine is high and the source is limited, resulting in high production costs, so it is...

AI Technical Summary

Problems solved by technology

[0004] The disadvantage of the adenosine method is that the price of adenosine is high and the source is limited, resulting in high production costs, so it is not suitable for large-scale industrial production

[0005] The disadvantage of hypoxanthine is that hypoxanthine is obtained by cleavage of inosine, therefore, the same price is higher and the source is limited, and the same production cost is higher and is not suitable for industrialized large-scale production

[0007] The disadvantage of this method is that the yield is extremely low, especially the yields of the two methods for preparing adenine from 4,6-dichloro-5-nitropyrimidine are less than 50%, and the chlorination of phosphorus oxychloride and Nitrification will produce a large amount of waste liquid, resulting in greater environmental pollution, which is also not suitable for industrialized large-scale production