Structure Determination and Conformational Analysis of Tofacitinib

OBJECTIVE To investigate the structure and conformation of synthesized Tofacitinib. METHODS The ¹H-NMR,¹H-NMR(DMSO-d6+D₂O),¹³C-NMR(at room and elevated temperature of 60 and 120℃), ¹H-¹H COSY, DEPT, HSQC, HMBC spectra of Tofacitinib and ¹³C-NMR of its key intermediate at room temperature were recorded in DMSO-d6. Based on the related literature, monograph and the ¹³C-NMR comparison of Tofacitinib and its key intermediate, the structure and conformation analysis of synthesized Tofacitinib in DMSO-d6 were carried out. RESULTS The structure of synthesized Tofacitinib was determined on the basis of these spectral data. Most of the signals of Tofacitinib in ¹³C-NMR spectrum at room temperature were split while these split signals were merged when the temperature was increased to 120℃. It maight have two conformations in DMSO-d6 at room temperature due to the restricted rotation about the carbon-nitrogen bond of the amide group. CONCLUSION The structure of synthesized Tofacitinib is confirmed and it may have two conformations in DMSO-d6 at room temperature.