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.
[Marsham, Peter R.; Hughes, Leslie R.; Jackman, Ann L.; Hayter, Anthony J.; Oldfield, John; et al. Journal of Medicinal Chemistry, 1991 , vol. 34, # 5 p. 1594 - 1605]
![diethyl N-[5-[N-(tert-butoxycarbonyl)-N-methylamino]-2-thenoyl]-L-glutamate结构式](https://image.chemsrc.com/caspic/398/132463-33-3.png)
![N-[5-[N-[(3,4-二氢-2-甲基-4-氧-6-喹唑啉基)甲基]-N-甲基氨基]-2-噻吩甲酰]-L-谷氨酸二乙酯结构式](https://image.chemsrc.com/caspic/067/132463-02-6.png)