Preparation method of 5-methylpyrazine-2-carboxylic acid

Abstract

The invention relates to an improved preparation method of 5-methylpyrazine-2-carboxylic acid. The method comprises the following steps of: carrying out an oxidation reaction in an acetic acid solvent by using 2,5-dimethylpyrazine as raw materials, cobalt acetate and manganese acetate as catalysts and potassium bromide as a cocatalyst, wherein the temperature of the oxidation reaction is 90-110 DEG C; when a small quantity of unreacted 2,5-dimethylpyrazine is detected to be still in the reaction system, ending the oxidation reaction; and cooling reaction liquid obtained after the oxidation reaction is ended, crystallizing, filtering and drying to obtain the 5-methylpyrazine-2-carboxylic acid, wherein the 2,5-dimethylpyrazine is prepared by using isopropanolamine as raw materials, introducing H2 and N2 in the presence of an activated Al-Cu-Ag-Zn catalyst at 200-280 DEG C for a continuous feeding reaction and simply distilling the reaction liquid. The method has easy obtaining of raw materials, simple and convenient operation, short step, good product quality and low product cost and is more suitable for industrial production.

Description

technical field The present invention relates to a preparation method of an intermediate of a pharmaceutical raw material drug, in particular to a preparation method of 5-methylpyrazine-2-carboxylic acid. 5-Methylpyrazine-2-carboxylic acid is a pharmaceutical raw material drug " An important intermediate of "Acipimox" and "Glipizide". Background technique 5-Methylpyrazine-2-carboxylic acid is an important intermediate of pharmaceutical raw materials "Acipimox" and "Glipizide". Acipimox is a drug for treating hypertriglyceridemia, hypercholesterolemia, and hypertriglyceridemia combined with hypercholesterolemia, and glipizide is a second-generation sulfonylurea hypoglycemic drug. The preparation method of existing 5-methylpyrazine-2-carboxylic acid mainly contains following several kinds: The first is to use cis-2,3-diamino-2-butene-1,4-dinitrile as raw material, through cyclization with aceguvaldehyde and hydrolysis with sulfuric acid to obtain 2-methylpyrazine-5,6-dinit...

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Problems solved by technology

The operation steps of this synthetic route are also relatively complicated, and because potassium permanganate is used for oxidation, the cost is higher, and potassium permanganate has a strong oxidation ability, so the selectivity is poor, and it is easy to be deeply oxidized, resulting in not very good product quality, and also not Suitable for industrial production

As mentioned above, most of the existing methods for preparing 5-methylpyrazine-2-carboxylic acid have shortcomings such as long steps, complicated operation, low yield or high cost, and are not suitable for industrial production.

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