Method for synthesizing 2-amido-6-chloropurine

Abstract

The present invention relates to a kind of synthesis method of 2-amino-6-chloropurine (1), comprising the following steps in turn: first drop phosphorus oxychloride into N,N-dimethylformamide at low temperature to form a mixed solution, Then drop into the 1,2-dichloroethane of guanine (2) and react to obtain 2-dimethylaminomethenimino-6-chloropurine (3); the reaction product (3) is dropped into water, and The organic phase is recovered and used mechanically, the pH of the aqueous phase is adjusted to 3 to 5 with an alkali metal hydroxide solution, and the reaction is heated to obtain a wet product of 2-formylamino-6-chloropurine (4); the wet product of the above reaction product (4) is then The hydrolysis reaction is carried out in an alkali metal hydroxide solution, and then the pH value is adjusted with hydrochloric acid to obtain the crude product of 2-amino-6-chloropurine (1), and finally purified to obtain the fine product of the target product (1).

Description

technical field [0001] The present invention relates to the synthesis method of 2-amino-6-chloropurine, 2-amino-6-chloropurine is an important intermediate for synthesizing the antiviral drug "Famciclovir" (Famciclovir), and can also be used for anticancer, anti-inflammatory and hypotensive Synthesis of other drugs. Background technique [0002] The English name of "Famciclovir" is Famciclovir, and its chemical name is 2-[2-(2-amino-9H-purin 9-yl)ethyl]-1,3-propanediol-diethyl ester. The anti-herpes virus drug is mainly used for the treatment of herpes zoster and genital herpes. Its structural formula is as follows: [0003] [0004] And 2-amino-6-chloropurine is a very important pharmaceutical intermediate for the synthesis of "Famciclovir". There are many synthetic routes of 2-amino-6-chloropurine, and the disclosed synthetic routes are listed as follows: [0005] 1. Direct Chlorination of Guanine [0006] Patent WO93 / 15075 publicly reported that 2-amino-6-chloropu...

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Problems solved by technology

[0013] Compared with the aforementioned several synthetic methods, although the process is relatively reasonable and the product yield is relatively high, which can reach 60% to 70%, there are still some deficiencies, such as in the synthesis of guanine and N, N-di In this step reaction that methyl formamide generates 2-dimethylaminomethenimino-6-chloropurine under the action of chlorinating agent, owing to adopting the mode that all raw materials are added together, be unfavorable for N on the one hand, N-di Methylformamide reacts with phosphorus oxychloride first to generate the active intermediate of carbanion, and then participates in the following reaction with guanine. On the other hand, it is easy to cause side reactions between guanine and chlorinating agent, so that the The product yield of step reaction is not high, and finally affects the yield and the purity of target product 2-amino-6-chloropurine; -6-Chloropurine (3) is separated from the reaction solution, and the reaction solution of this step reaction needs to be subjected to post-treatment operations such as pH adjustment and suction filtration, and the process is complicated; and because the material is viscous, suction filtration is also very difficult

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