Study On The Synthesis Of Raltitrexed

The present situation of colorectal cancer was reviewed briefly in this paper. The therapeutical function and the drugs in clinical research of thymidylate synthase inhibitor were summarized in detail. The pharmacological peculiarity of raltitrexed, a thymidylate synthase inhibitor, was introduced.The synthetic methods for raltitrexed were investigated and an economical and reasonable synthetic route was studied. The target compound was synthesized with a total yield of 12.9% from 2-thiophenealdehyde via eleven steps of reaction, such as nitration, oxidation, esterification, reduction, protection, N-methylation, hydrolysis, condensation, deprotection, N-alkylation, hydrolysis. The synthetic procedure of the intermediate was studied intensively and optimized. The operation was simplified and could be practical in a large scale. All the materials are available domestically.The structure of raltitrexed was confirmed by ~1H-NMR spectrum and mass spectrum.