摘要
Raltitrexed (8), a new quinazoline-based inhibitor of thymidylate synthase (TS), has been registered widely for the first-line treatment of advanced colorectal cancer. [1,2] As reported in the literature, [3,4] it can be prepared from 2-thiophenecarboxylic acid via 7 steps in 3% overall yield, but n-BuLi and the low temperature at - 78 ℃ was needed for the introduction of 5-carboxyl group into thiophene ring through lithiation of 2-(N-Boc-N-methylamino) thiophene followed by the addition of CO2. Here we wish to report a new route for the synthesis of Raltitrexed which was obtained from 2,5-thiophenedicarboxylic acid via 6 steps in 18.2% overall yield (Scheme 1). The mild conditions utilized in the synthetic route avoid the use of n-BuLi, NaH and the experimental conditions of low temperature at - 78 ℃ and strictly free of water, and are suitable for the large-scale preparation.……
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2003年第z1期220-220,共1页
Chinese Journal of Organic Chemistry
基金
Project supported by the Natural Science Foundation of Beijing City, the Education Committee of Beijing City and the Ministry of Education of China.