<p>The new type of catalytic one-pot Knoevenagel-Michael reaction was found: the direct chemical one-pot transformation of phenylglyoxal, barbituric acids, and pyrazoline-5-ones in the presence of a catalytic amount of <i>p</i>-TsOH and in alcohols with the formation of 6-hydroxy-5-[1-(5-hydroxy-3-methyl-1<i>H</i>-pyrazol-4-yl)-2-oxo-2-phenylethyl]pyrimidine-2,4(1<i>H</i>,3<i>H</i>)-diones has been found. This one-pot process is a very efficient and convenient way to substituted 6-hydroxy-5-[1-(5-hydroxy-3-methyl-1<i>H</i>-pyrazol-4-yl)-2-oxo-2-phenylethyl]pyrimidine-2,4(1<i>H</i>,3<i>H</i>)-diones—useful compounds for different biomedical applications—using reasonable and non-expensive starting materials. Mild and facile conditions of this catalytic multicomponent process lead to excellent substance yields together with a simple non-chromatographic isolation procedure.</p> Graphical abstract <p></p>