Method for synthesizing persantine intermediate 2,4,6,8-tetrahydroxy pyrimido[5,4-d] pyrimidine

Abstract

The invention relates to a method for synthesizing a persantine intermediate 2,4,6,8-tetrahydroxy pyrimido[5,4-d] pyrimidine, comprising the following steps of: (1) adding nitro orotic acid in an alkali liquid, then hydrogenating with Ni/H2, and filtering to obtain an amino orotic acid solution which is directly used for next reaction without separation; (2) adjusting pH of the amino orotic acid solution with concentrated hydrochloric acid to 3, adding sodium cyanate for temperature control reaction to obtain the urea derivatives of the amino orotic acid; then dropping a 30% sodium hydroxide solution to adjust pH to 13, heating for cyclization, dropping a 50-60% sulfuric acid solution to adjust pH to 3; (3) cooling to room temperature, filtering, washing to neutrality and drying to obtain the product. The intermediate of step (1) is not needed to separate, thereby saving a lot of time and labor, reducing about 50% of total reaction time with mild reaction condition and maximum reaction temperature reduced to 95 DEG C so that the device is less required and more durable.

Description

technical field [0001] The invention relates to a method for synthesizing a dipyridamole intermediate-2,4,6,8-tetrahydroxypyrimido[5,4-d]pyrimidine, which belongs to the field of organic chemistry. Background technique [0002] Dipyridamole, another name dipyridamole, dipyridamole is a non-nitrate coronary artery dilator, which can expand coronary blood vessels, promote the formation of collateral circulation and mild anticoagulation. Dipyridamole can be used for coronary heart disease, and as an anti-platelet aggregation drug to prevent thrombosis and disseminated intravascular coagulation. It can also be used in the treatment of nephropathy. It mainly plays the role of anti-blood viscosity and anti-thrombosis. 2,4,6,8-Tetrahydroxypyrimido[5,4-d]pyrimidine plays a very important role as an intermediate of dipyridamole. [0003] Related studies have been carried out abroad, such as Fisher, F.G.et al., Annalen, 1950,572,217, which reported a yield of 67%. The method used po...

AI Technical Summary

Problems solved by technology

[0010] The task of separating the aminoorotic acid obtained by hydrogenation in the first step is heavy, requiring the use of a plate and frame filter press, which is inefficient

Lead to long production cycle and high labor cost

[0011] The second step reaction needs to be reacted under the condition of urea melting, and the stirring is difficult

Moreover, the required reaction temperature is as high as 190°C, and the heating time is as long as 10 hours. These shortcomings lead to high equipment requirements, fast depreciation, and high energy consumption per unit product.

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