Preparation methods of 2,4-diamido-5-nitroso-6-hydroxypyridine and guanine

Abstract

The invention discloses a preparation method of 2,4-diamido-5-nitroso-6-hydroxypyridine. The preparation method comprises the following steps: (1) in a sodium methoxide methanol solution, carrying outa ring-closure reaction between methyl cyanoacetate and guanidine salt; (2) adding recycled absolute methanol to be diluted, filtering and recycling byproduct sodium nitrate; (3) concentrating a filter liquor, and recycling absolute methanol; (4) adding water to destroy excessive sodium methoxide, concentrating and recycling water-containing methyl alcohol; (5) in a diluted methane acid solution,carrying out a nitrosation reaction among an obtained concentrate, sodium nitrite and a nitrosation mother liquor; (6) after the reaction ends, carrying out cooling crystallization, filtering, takinga filter liquor as the nitrosation mother liquor to be used indiscriminately, and drying an obtained filter cake to obtain the 2,4-diamido-5-nitroso-6-hydroxypyridine. According to the preparation method, indiscriminate use of the nitrosation mother liquor and recycling of sodium nitrate and methyl alcohol are realized, and simultaneously the diluted methane acid solution is used for replacing concentrated sulfuric acid used, in the prior art, to carry out the nitrosation reaction, so that the recycling of a solvent and a reagent is facilitated, and the displacement of waste water is reduced.

Description

technical field [0001] The invention belongs to the technical field of preparation of key intermediates of lowe-type antiviral drugs and folic acid, and specifically relates to a preparation method of 2,4-diamino-5-nitroso-6-hydroxypyrimidine and guanine. Background technique [0002] Clovir drugs, mainly including acyclovir, ganciclovir, valacyclovir and faciclovir, are broad-spectrum antiviral drugs. It is clinically used to treat herpes simplex and diseases related to HSV infection. [0003] Folic acid, also called vitamin B9, is a water-soluble anti-anemia vitamin. Folic acid helps the metabolism of protein, and together with vitamin B12, promotes the production and maturation of red blood cells. [0004] 2,4,5-triamino-6-hydroxypyrimidine sulfate is an important intermediate for the synthesis of folic acid and Lovers, and nitrospyrimidine is the synthesis of 2,4,5-triamino-6-hydroxypyrimidine sulfate and The important intermediate of guanine, paper literature (Guangd...

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Problems solved by technology

[0008] Can produce a large amount of (accounting for 1 / 3~1 / 2 of recovery total amount) reclaim dilute formic acid solution on the one hand, the mass percent concentration of formic acid in this part dilute formic acid solution is generally below 65%, because this step cyclization reaction needs The concentration of formic acid needs to be above 70%, so the recovered dilute formic acid solution cannot be directly recycled in this step, and further treatment is required, which will inevitably greatly increase the preparation cost

[0009] On the other hand, a large amount of sodium formate (about 3 to 4 equivalents of 2,4,5-triamino-6-hydroxypyrimidine) needs to be used in this step, which further increases the preparation cost of guanine

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