A kind of synthetic method of pharmaceutical intermediate cycloalkane pyrimidinedione compound

Abstract

The invention provides a synthesis method of cycloalkane pyrimidine diketone compound, which belongs to the technical field of organic synthesis. The method provided by the present invention is to use 2-methoxycarbonyl cycloalkanone compound as a raw material, and in the presence of alkali to undergo a ring-closing reaction with S-methylisothiourea sulfate in water, and adjust the pH to generate a suspension after the reaction is completed , filtered to obtain the crude product of 2-methylthio-4 hydroxycycloalkane and pyrimidine compound, the crude product undergoes a hydrolysis reaction in the presence of an acid catalyst, and after the reaction is completed, heat filtration, solvent washing, vacuum concentration, crystallization, filtration, water washing, Operations such as drying obtain the target product cycloalkanopyrimidinedione compound. The synthesis method of the invention has high yield, simple and convenient operation, is friendly to equipment and environment, and is suitable for efficient synthesis of cycloalkane pyrimidine diketone compounds.

Description

technical field [0001] The invention relates to a synthesis method of a pharmaceutical intermediate cycloalkane pyrimidine diketone compound, which belongs to the technical field of organic synthesis. Background technique [0002] Cycloalkanopyrimidinedione structures are an important class of active groups, which exist in a variety of chemical drugs and have a wide range of biological activities. They play a very important role in drug design and functional group modification. The development of synthetic methods for cycloalkanepyrimidinedione compounds has attracted increasing attention in the industry. Researchers have conducted a lot of research on it and achieved certain results. The cyclization of 2-oxocycloalkylcarboxylate compounds with urea Obtaining cycloalkane pyrimidine diketone compound is a commonly used method, which has the advantage of simple route, but the yield of this method is mostly not high, and the reaction yield of 2-oxocycloalkyl carboxylate compoun...

AI Technical Summary

Problems solved by technology

The development of synthetic methods for cycloalkanepyrimidinedione compounds has attracted increasing attention in the industry. Researchers have conducted a lot of research on it and achieved certain results. The cyclization of 2-oxocycloalkylcarboxylate compounds with urea Obtaining cycloalkane pyrimidine diketone compound is a commonly used method, which has the advantage of simple route, but the yield of this method is mostly not high, and the reaction yield of 2-oxocycloalkyl carboxylate compounds of different structures The difference is very large, except for a few reaction yields that can reach more than 90%, most of them are between 30-70%, or even as low as 15%, which not only wastes a lot of raw material reagents, but also causes difficulties in post-processing, such as Purification methods such as column chromatography greatly complicate the separation and purification process, thereby greatly increasing production costs and environmental pollution

In addition, another optional method is to first synthesize 2-mercapto-4-hydroxypyrimidine compound, and then hydrolyze the mercapto group under the catalysis of strong acid such as hydrochloric acid to obtain cycloalkanepyrimidinedione compound. This method generally has a higher yield, but requires Using a large excess of hydrochloric acid and other corrosive and volatile strong acids will not only seriously corrode the equipment during the long-term high-temperature reaction process, but also easily cause serious environmental pollution

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