New Synthesis of Thymidylate Synthase Inhibitor Raltitrexed

Abstract

The quinazoline-based inhibitor of thymidylate synthase, Raltitrexed, was synthesized from 2,5-thiophenedicarboxylic acid via mono-coupling with diethyl l -glutamate, modified Curtius reaction, N-methylation, removal of Boc-protecting group, condensation with (bromomethyl)quinazolinone and saponification in 18.2% overall yield.

Keywords:

• Thymidylate synthase inhibitor
• Raltitrexed
• Synthesis

Acknowledgments

We are grateful to the Natural Science Foundation, the Education Committee of Beijing City, and the Ministry of Education of P. R. China for financial support.