Method for synthesizing 2-methyl-4-amino-5-formamide methyl pyrimidine

Abstract

The invention discloses a method for synthesizing 2-methyl-4-amino-5-formamide methyl pyrimidine. The method comprises the following steps: conveying an organic ester solvent solution with beta-aminopropionitrile and an organic alcohol solution with sodium alcoholate into a pipeline reactor, performing a continuous reaction, discharging the materials, performing cooling, performing neutralizationto neutral, performing vacuum recycling on a solvent, continuously adding methylbenzene, and performing water washing so as to obtain a methylbenzene solution of 2-formyl-3-formyl amino-propionitrile;adding acetamidine hydrochloride into the organic alcohol solution with sodium alcoholate, performing filtration after addition, collecting filtrate, performing heating, putting the methylbenzene solution of 2-formyl-3-formyl amino-propionitrile; and adding acetamidine hydrochloride into the filtrate, under a vacuum condition, evaporating out the solvent and adding an alcohol of a corresponding volume at the same time, stopping the reaction when a solution of a volume equal to that of the organic alcohol solution with the sodium alcoholate is evaporated out, performing neutralization to neutral, performing vacuum crystallization, performing filtering, and performing drying, so as to obtain the compound. The method is simple, gentle in reaction condition, low in reaction equipment requirement, low in cost and high in yield.

Description

technical field [0001] The invention relates to the field of compound synthesis methods, in particular to a synthesis method of 2-methyl-4-amino-5-carboxamidomethylpyrimidine. Background technique [0002] 2-Methyl-4-amino-5-carboxamidomethylpyrimidine is an important intermediate in the synthesis of vitamin B1, and its molecular formula is as follows: [0003] [0004] The existing domestic main synthetic techniques all use β-aminopropionitrile as the raw material, undergo high-pressure reaction to obtain enol sodium salt, and then carry out cyclization reaction with acetamidine to obtain 2-methyl-4-amino-5-carboxamidomethylpyrimidine . The current process used to synthesize enol sodium salt is high-pressure reaction, the reaction pressure is in the range of 3-6MPa, and the product is solid. In the large-scale production process, the cost of large-scale high-pressure equipment and maintenance costs are high, and there is a certain risk. . [0005] Among them, the pate...

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Problems solved by technology

The current process used to synthesize enol sodium salt is high-pressure reaction, the reaction pressure is in the range of 3-6MPa, and the product is solid. In the large-scale production process, the cost of large-scale high-pressure equipment and maintenance costs are high, and there is a certain risk.

[0005] Among them, the patent application US4716243A uses enol sodium salt as raw material, forms enamine with o-chloroaniline, and then reacts with acetamidine to obtain the product. , there is a risk of end product residue, and the cost of recycling o-chloroaniline is relatively high

Patent application CN103420918A adopts enol sodium salt to directly react with acetamidine, and under the action of Lewis acid such as zinc chloride, directly obtains the product formylpyrimidine, and the highest yield can reach 74%, but uses Lewis acid such as zinc chloride as a catalyst , the amount of which is about 0.15-0.3 equivalents, the cost is high, and in the post-treatment process, the by-product zinc hydroxide precipitates, and the separation is difficult in the industrial production process

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