Regioselective addition reactions at C-2 of 3,4-dihydropyrimidinones. Synthesis and evaluation of multifunctionalized tetrahydropyrimidines

Multifunctionalized tetrahydropyrimidines derivatives have been synthesized from Biginelli 3,4-dihydropyrimidin-2-(1H)-thiones (DHPMs) efficiently. The transformation includes desulfurization of DHPMs with Raney-Ni and subsequent regioselective C-2 functionalization using a variety of C-nucleophiles with simultaneous activation with ethyl chloroformate. Functionalized pyrimidine derivatives containing bulky substituents at C-2 of the pyrimidine ring are cytostatic.

Graphical abstractMultifunctionalized tetrahydropyrimidines derivatives bearing bulky C-2 substituents are cytostatic and inhibit proliferation of murine leukemia, murine mammary carcinoma, human T-lymphocyte and human cervix carcinoma cells.Figure optionsDownload full-size imageDownload as PowerPoint slide