摘要
目的鉴定合成的托法替尼的化学结构,并对其构象进行分析。方法用DMSO-d6作溶剂,通过测试该合成样品的~1H-NMR、~1H-NMR(DMSO-d6+D_2O)、^(13)C-NMR(包括常温、高温60℃、高温120℃的图谱)、~1H-~1H COSY、DEPT、HSQC、HMBC图谱及其关键中间体的常温^(13)C-NMR图谱,参照文献与专著,鉴定合成的托法替尼的化学结构,并分析其构象。结果确证了合成的托法替尼的化学结构。其常温^(13)C-NMR图谱中,大多数信号出现裂分,升温到120℃,裂分信号合并,推导在常温下,因为围绕酰胺键的旋转受阻,托法替尼在DMSO-d6溶液中以2种构象存在。结论合成的托法替尼结构正确,且常温下在DMSO-d6溶液中以2种构象存在。
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.
作者
张霞
章国龙
ZHANG Xia;ZHANG Guolong(Huadong Medicine Group Pharmaceutical Research Institute Co.,Ltd.,Hangzhou 310011,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2019年第5期542-544,共3页
Chinese Journal of Modern Applied Pharmacy
关键词
托法替尼
构象
核磁共振
关键中间体
受阻旋转
Tofacitinib
conformation
nuclear magnetic resonance
key intermediate
restricted rotation
