Synthetic process of 2-methyl-5-carboxylic acid pyrazine

Abstract

The invention provides a method for preparing 2-methyl-5-pyrazinecarboxylic acid. The method provided by the invention is characterized in that potassium permanganate which is more harmful to the environment is not used, a target compound 2-methyl-5-pyrazinecarboxylic acid can be prepared from cheap and easily available methylglyoxal and 2-amino malonamide taken as raw materials through four stepsof cyclization, hydrolysis, chlorination and reduction, the yield of the reaction route is high, the amount of byproducts is small, and products are purer.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a synthesis process of 2-methyl-5-carboxylic acid pyrazine. Background technique [0002] 2-Methyl-5-carboxylic acid pyrazine is an important pharmaceutical intermediate, which is mainly used to prepare the important hypoglycemic drug glipizide and a new generation of long-acting hypolipidemic drug acipimox. At the same time, its derivatives Methyl 2-methyl-5-pyrazinecarboxylate is also an important drug for the treatment of tuberculosis. [0003] At present, for the synthesis of this compound, there are mainly the following two types: [0004] 1) Prepared by decarboxylation of 2-methyl-5,6-dicarboxylic acid pyrazine [0005] [0006] Specifically, the preparation of 2-methyl-5,6-dicarboxylic acid pyrazine has the following two methods: [0007] A. Preparation with aceglyoxal and o-phenylenediamine as raw materials [0008] [0009] B. Prepared from maleonitrile and methylglyoxa...

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Problems solved by technology

[0011] Specifically, the problem of the first method is that the process route is long, the yield of oxidation and decarboxylation is low, and potassium permanganate, which is harmful to the environment, is used, which produces a large amount of manganese-containing waste residue, and the treatment cost is high

Although the second method can avoid the use of potassium permanganate, its main raw material diaminomaleonitrile is difficult to synthesize, the cost is high, and the decarboxylation yield is low. It is reported that the yield is only 53%, which is not suitable for large-scale Production

[0015] At present, this route is a relatively commonly used synthesis method in production. The main problem of this route is that potassium permanganate is used as an oxidant, and a large amount of water needs to be added for the reaction, which will produce a large amount of manganese-containing waste residue and waste water; meanwhile, this route is due to Using 2,5-dimethylpyrazine with a symmetrical structure as a raw material, the selectivity of its oxidation is relatively poor, and a large amount of double oxidation products are produced, and the total yield is low. It is reported in the literature that the yield is only 5.8%. The purification process complex

[0016] As mentioned above, the existing synthetic methods for the preparation of 2-methyl-5-carboxylic acid pyrazine have the disadvantages of not being environmentally friendly, low yield, and difficult purification, so it is necessary to develop a more suitable synthetic process

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