LAUSR

Abstract A general and efficient synthetic method for 6-unsubstituted 3,4-dihydropyrimidin-2(1H)-thiones 6 and -ones 7 has been developed. In three-component reactions, the reactivity of reagents serving as the C5–C6 fragment of the dihydropyrimidine ring was compared. The reaction of thiourea or urea 12, aldehydes 13, and ethyl 3-dimethylaminoacrylate 9 in the presence of a catalytic amount of AlCl3 by heating smoothly proceeds to give 6 and 7 in high yields. A synthetic novelty of our protocol is as follows: 1) Lewis acid-mediated reaction, 2) good to high yields, 3) broad scope as for aldehydes, and ureas. Hitherto unavailable 6-unsubstituted 2-aminodihydropyridimidine 8 has been obtained from the 2-thioxo derivative 6 by a stepwise method involving a substitution reaction with the amine at the 2-position. These 6-unsubstituted compounds 6, 7, and some 6-methyl derivatives 16 were assessed for their antiproliferative effect on the human promyelocytic leukemia cell line, HL-60. The 4-propyl-6-methyl derivative 16b showed relatively strong activity with the IC50 value of 952 nM.