Jiaojiao Xu, Jin Cai, Jun-qing Chen
Apr 1, 2016
Citations
3
Influential Citations
13
Citations
Journal
Journal of Chemical Research
Abstract
A highly efficient method for the synthesis of baricitinib was developed. The starting material tert-butyl 3-oxoazetidine-1-carboxylate was converted to intermediate 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile via the Horner–Emmons reaction, deprotection of the N-Boc-group and a final sulfonamidation reaction. Then the nucleophilic addition reaction was carried out smoothly to afford the borate intermediate in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene under reflux. Finally, the desired compound baricitinib was obtained by the Suzuki coupling reaction of 4-chloro-7-H-pyrrolo[2,3-d]pyrimidine with the above borate intermediate. All compounds were characterised by IR, MS, 1H NMR and 13C NMR. The overall yield in this synthetic route was as high as 49%. Moreover, this procedure is straightforward to carry out, has low cost and is suitable for industrial production.