A kind of synthetic method of 2-amino-6-chloropurine

Abstract

The invention provides a method for synthesizing 2-amino-6-chloropurine, which belongs to the field of organic synthesis. The synthetic method provided by the present invention comprises the following steps: adding 2-acetylamino-6 hydroxypurine, hexachloroacetone, organic base and thionyl chloride to the reaction vessel, heating to reflux for 2h-48h, distilling off thionyl chloride, Add lye A, react for 1h-12h, adjust the pH value to 7.0-7.5, separate and purify, and obtain the target product 2-amino-6-chloropurine. The invention greatly reduces the use of nitrogen- and phosphorus-containing reagents, correspondingly reduces the discharge of nitrogen- and phosphorus-containing waste water, and is beneficial to large-scale process production.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a method for synthesizing 2-amino-6-chloropurine. Background technique [0002] 2-Amino-6-chloropurine is a white powdery solid, insoluble in water, easily soluble in sodium hydroxide solution, and is an important pharmaceutical intermediate. In current applications, 2-amino-6-chloropurine is mainly used to produce a series of antiviral drugs such as Penciclovir and Famciclovir. In some literature reports, 2-amino-6-chloropurine can also be used to synthesize anticancer drugs, anti-inflammatory drugs and blood pressure lowering drugs. [0003] In the prior art, the synthesis methods of 2-amino-6-chloropurine mainly include chlorine gas spray method, direct chlorination method and first amino protection and then chlorination method. [0004] Wherein, the chlorine gas spray method is to be raw material with guanine and phosphorus pentasulfide, then sprays with chlorine gas, just ...

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Problems solved by technology

[0004] Wherein, the chlorine gas spray method is to be raw material with guanine and phosphorus pentasulfide, then sprays with chlorine gas, just obtains target product, but the decomposition product of phosphorus pentasulfide that this method uses can produce peculiar smell, pollutes environment, and thioguanine does not Stable, so the product yield is between 50%-60%

[0005] The direct chlorination method uses guanine and phosphorus oxychloride as raw materials to react in the presence of a phase transfer catalyst. The synthesis method is simple in process and simple in reaction, but the yield is low, only about 30%-42%.

[0006] The first amino protection rechlorination method mainly contains two paths, the first path is that guanine and DMF react in the presence of phosphorus oxychloride to obtain an intermediate product and then hydrolyze to obtain 2-amino-6-chloropurine, although this path It is convenient and efficient, but it will produce a large amount of phosphorus- and nitrogen-containing wastewater, which is not conducive to industrial applications; the second path is to acetylate guanine first to obtain 2,9-diacetylguanine and then chlorinate it with phosphorus oxychloride. The target product can be obtained by removing the acetyl group at the 9-position by hydrolysis, but there are two problems in this route. One is that the reaction time of guanine acetylation is too long, and it usually takes more than ten hours to complete the reaction. Phosphorus as a chlorinating agent will result in wastewater with a high phosphorus content

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