The methylation of 4,5-dihydroorotic acid benzyl ester (I) with methyl iodide gives the corresponding 1-methyl derivative (II), which is debenzylated by hydrogenolysis with H2 over Pd/C yielding (S)-1-methyl-4,5-dihydroorotic acid (III). Finally, this compound is condensed with L-histidyl-L-prolinamide (IV) by means of dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (HONSU) in DMF.