Solvent-Free Synthesis and Antiviral Activity of Chiral Dialkyl 2-(Substituted-((4-(Pyridin-3-Yl)Pyrimidin-2-Yl)Amino)Methyl) Malonate

An efficient asymmetric synthesis of chiral β-amino acid ester derivatives containing a 4-(pyridin-3-yl)pyrimidin-2-yl amine moiety was developed. This catalytic asymmetric Mannich reaction gave target products in high yields (95%) and excellent enantioselectivities (>99% ee) using a cinchona-based squaramide catalyst under solvent-free, one-pot conditions. Antiviral bioassays indicated that some of the chiral products exhibited higher antiviral activities against tobacco mosaic virus than the commercial compound ribavirin.