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• Novel 6-unsubstituted 2-aminodihydropyrimidines were synthesized. • The amination reaction was mediated by a catalytic amount of Sc(OTf) 3. • 2-Aminodihydropyrimidines with different substituent patterns at the 4- and 6-positions were synthesized. • The antiproliferative effect of the compounds on HL-60 cells was explored. • The 2-benzyl derivative showed high activity with an IC 50 < 100 nM. An efficient method of synthesis of novel 6-unsubstituted 2-aminodihydropyrimidines 9 has been developed. The substitution reaction of 2-methylthiodihydropyrimidines 7 and primary amines in the presence of a catalytic amount of Sc(OTf) 3 with heating proceeds smoothly to give 9 in good to high yields. This amination protocol can be applied to various aryl- and alkylamines. Other 2-methylthiodihydropyrimidines 10 having different substituent patterns at 4- and 6-positions also reacted with aniline under the same conditions to give corresponding 2-anilinodihydropyrimidines 11 in high yields. These compounds 9 were assessed for their antiproliferative effect on the human promyelocytic leukemia cell line HL-60. The 2-benzyl derivative 9i showed a relatively high activity with an IC 50 of <100 nM. The high activity of 9i was comparable to that of all- trans retinoic acid (223.1 nM). The results of the trypan blue exclusion test of 9i indicated that necrosis-like cell death occurred. [ABSTRACT FROM AUTHOR]