文献类型：期刊文献

英文题名：A practical synthesis for the key intermediate of apixaban

作者：Dong, Wenwen[1];Gong, Tengfei[1];Liu, Chaoyang[1];Lin, Jia[1];Jia, Qiang[2];Chu, Changhu[1]

机构：[1]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Shanghai Key Lab New Drug Design,Minist Educ, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Seasons Biotechnol Taizhou Co Ltd, 21 Jiutiao Rd, Taizhou 318000, Zhejiang, Peoples R China

年份：2024

卷号：155

期号：1

起止页码：99

外文期刊名：MONATSHEFTE FUR CHEMIE

收录：;EI(收录号：20235015216091);WOS:【SCI-EXPANDED(收录号:WOS:001122302600001)】；

基金：This work was supported by the National Natural Science Foundation of China (21372081, 21172072).

语种：英文

外文关键词：Apixaban intermediate; Synthesis; Amine oxidation; Sodium chlorite

摘要：Apixaban is a highly potent, selective, and efficacious inhibitor of blood coagulation factor Xa. A practical and efficient process has been developed for the preparation of the key intermediate of apixaban. Starting from inexpensive 4-chloronitrobenzene and piperidine, an eight-step procedure for the intermediate has been developed. In this case, sodium chlorite is used twice to oxidize the piperidine cycle to the corresponding lactam under a CO2 atmosphere, resulting in the construction of two lactams. Furthermore, most of these reactions are highly efficient and practical as they occur under mild conditions. Most of the intermediates can be obtained through simple slurry or recrystallization, and column chromatography purification is not necessary.