Base-Mediated Biginelli-Like Reaction Ignited by Aromatic Isocyanate: A Facile One-Pot Synthesis of N⁴-Aryl-5-carboxyl-6-methyl Cytimidine Derivatives

Abstract

The new three-component Biginelli reaction of aromatic isocyanate, ethyl acetoacetate, and substituted urea (or thiourea as well as guanidine) is described for the first time. In this reaction, N ⁴-aryl-5-carboxyl-6-methyl cytimidine derivatives were obtained in moderate to excellent yields by employing DBU as a highly effective catalyst. This methodology provides several advantages such as good functional group tolerance, excellent yields, atom efficiency, and experimental simplicity.

GRAPHICAL ABSTRACT

Keywords:

• Biginelli reaction
• isocyanate
• multicomponent reaction
• pyrimidine

ACKNOWLEDGMENTS

We thank Dr. Biing-Jiun Uang from National Tsing Hua University and Dr. Qixing Zhong from National University of Singapore for their generous assistance in the preparation of this manuscript. We appreciate the support from Center for Instrumental Analysis, China Pharmaceutical University, for their contribution in the structural confirmation.