Development of industrial process for the synthesis of the active pharmaceutical ingredient "6-Methyluracil"

Abstract

In this work, preparative approaches to the synthesis of the active pharmaceutical ingredient, 6-methyluracil, and intermediate compounds have been considered. Known synthesis methods were characterized to evaluate the possibility of their use under industrial conditions and scaling. The most promising conditions for obtaining target substances and the possibility of scaling chemical stages and processes have been verified. We established the conditions for the two-stage synthesis of 6-methyluracil based on commercially available raw materials, acetoacetic ethyl ester and urea. At the first stage, water was azeotropically distilled with hexane as a solvent under the catalysis by para-toluenesulfonic acid, and the corresponding ethyl ureidocrotonate was obtained. 6-Methyluracil was prepared by heating ethyl ureidocrotonate with aqueous alkali followed by the addition of hydrochloric acid to the reaction mixture. The industrial process for the synthesis of 6-methyluracil was created and tested.