Method for synthesizing 2,4-diamino-6-chloropyrimidine

Abstract

The invention discloses a method for synthesizing 2,4-diamino-6-chloropyrimidine. According to the method, methyl cyanoacetate, guanidine nitrate and sodium methoxide serve as raw materials to react with one another to obtain 2,4-diamino-6-hydroxypyrimidine, and then 2,4-diamino-6-hydroxypyrimidine is chloridized with POCl3 in the presence of triethylamine to obtain 2,4-diamino-6-chloropyrimidine.Compared with the prior art, the situation that the whole reactant is neutralized to generate and precipitate a large amount of phosphate is avoided, the product purity is improved, the product yieldis increased, the situation that a solvent is used for refining DACP is avoided, the process is greatly simplified, the cost is reduced, the yield is increased, and the method has the advantages of being high in yield, easy to operate and high in safety and is a very effective process suitable for industrialized mass production.

Description

technical field [0001] The invention relates to the technical field of medicine manufacture, in particular to a synthesis method of 2,4-diamino-6-chloropyrimidine. Background technique [0002] 2,4-diamino-6-chloropyrimidine (DACP) is the main raw material for the synthesis of Minoxidil, and is also used as an auxiliary material in the electrolysis industry. Some methods for preparing DACP have been reported in the literature, and most of the yields are Low cost, high cost, cumbersome process, according to the description of European patent EP0295218, it is like this: add sodium methylate to alcohol, after cooling down, add guanidine hydrochloride and ethyl cyanoacetate while stirring, then heat and reflux for 2 hours, distill off the solvent, Add water, then adjust pH=8 with hydrochloric acid, cool, filter, and dry to obtain 2,4-diamino-6-hydroxypyrimidine (DAHP) with a yield of 79.6%. [0003] Then add 2,4-diamino-6-hydroxypyrimidine (DAHP) in phosphorus oxychloride, refl...

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Problems solved by technology

[0002] 2,4-diamino-6-chloropyrimidine (DACP) is the main raw material for the synthesis of Minoxidil, and is also used as an auxiliary material in the electrolysis industry. Some methods for preparing DACP have been reported in the literature, and most of the yields are Low cost, high cost, cumbersome process, according to the description of European patent EP0295218, it is like this: add sodium methylate to alcohol, after cooling down, add guanidine hydrochloride and ethyl cyanoacetate while stirring, then heat and reflux for 2 hours, distill off the solvent, Add water, then adjust pH=8 with hydrochloric acid, cool, filter, and dry to obtain 2,4-diamino-6-hydroxypyrimidine (DAHP), with a yield of 79.6%

[0006] Chinese patent CN10566230A describes: 15g DAHP is added to 45ml phosphorus oxychloride to obtain 5.32g DACP, the yield is 31%, and the yield is extremely low

[0007] When we synthesized DACP, we found that according to the above data, the following disadvantages generally existed: the yield of DACP prepared by DAHP was low, and the operation was complicated, especially after chlorination and neutralization pH=8

Because a large amount of hydrogen phosphate 6-8 times that of DACP is produced into phosphate, which is precipitated at the same time as the product, so the separation of impurities and products is a great problem. No experiment can easily and stably obtain the product, and a large number of uses Solvents, troublesome to operate, and costly

We have repeated countless experiments but can't get the desired effect

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