特立氟胺的合成工艺改进
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摘要
以氰乙酸为原料,通过氯化、酰胺化、C-酰化反应等合成特立氟胺,总收率为81. 7%,产物经NMR和HRMS等谱图确证。该工艺原料易得,条件温和,产率较高,适合工业化生产。
Teriflunomide was synthesized by a serial reactions of chlorination,amidationand C-acylationfrom cyanoacetic acid. The overall yield was about 81. 7%,and the structure of the product was confirmed by NMR and HRMS. The process route is easy to obtain raw materials with mild conditions and high yield. Thus it is suitable for industrial production.
Teriflunomide was synthesized by a serial reactions of chlorination,amidationand C-acylationfrom cyanoacetic acid. The overall yield was about 81. 7%,and the structure of the product was confirmed by NMR and HRMS. The process route is easy to obtain raw materials with mild conditions and high yield. Thus it is suitable for industrial production.
引文
[1]Gold R,Wolinsky J S. Pathophysiology of multiple sclerosisand the place of teriflunomide[J]. Acta NeurologicaScandinavica,2011,124(2):75-84.
[2]Zeyda M,Poglitsch M,Geyeregger R,et al. Disruption ofthe interaction of t cells with antigen-presenting cells bythe active leflunomide metabolite teriflunomide:Involvement of impaired integrin activation and immunologicsynapse formation[J]. Arthritis Rheum,2005,52(9):2730-2739.
[3]徐鲁杰,鲜文颖,邵华.多发性硬化症的治疗新药———特立氟胺[J].药学与临床研究,2014,22(2):158-162.
[4]Faragher R J,Motto J M,Kaminski M A,et al. A convenientsynthesis of13C4-Leflunomide and its primary metabolite13C4-A771726[J]. Journal of Labelled Compounds&Radiopharmaceuticals,2003,46(7):613-622.
[5] Hirth KP,Schwartz DP,Mann E,et al. Treatment ofplatelet derived growth factor related disorders such ascancers[P]. US5700823A,1997-12-23.
[6]石静波,张茜,金涌,等.特立氟胺的合成研究[J].中国药学杂志,2008,43(17):1353-1354.
[7]巨修练,杜嘉文,邓艳丽.氟立特胺的制备方法[P].中国103709068A,2014-04-09.
[8]薛昊,耿穎姝,牛磊,等.免疫调节剂特立氟胺的合成工艺改进[J].中国药物化学杂志,2017,27(1):43-45.
[2]Zeyda M,Poglitsch M,Geyeregger R,et al. Disruption ofthe interaction of t cells with antigen-presenting cells bythe active leflunomide metabolite teriflunomide:Involvement of impaired integrin activation and immunologicsynapse formation[J]. Arthritis Rheum,2005,52(9):2730-2739.
[3]徐鲁杰,鲜文颖,邵华.多发性硬化症的治疗新药———特立氟胺[J].药学与临床研究,2014,22(2):158-162.
[4]Faragher R J,Motto J M,Kaminski M A,et al. A convenientsynthesis of13C4-Leflunomide and its primary metabolite13C4-A771726[J]. Journal of Labelled Compounds&Radiopharmaceuticals,2003,46(7):613-622.
[5] Hirth KP,Schwartz DP,Mann E,et al. Treatment ofplatelet derived growth factor related disorders such ascancers[P]. US5700823A,1997-12-23.
[6]石静波,张茜,金涌,等.特立氟胺的合成研究[J].中国药学杂志,2008,43(17):1353-1354.
[7]巨修练,杜嘉文,邓艳丽.氟立特胺的制备方法[P].中国103709068A,2014-04-09.
[8]薛昊,耿穎姝,牛磊,等.免疫调节剂特立氟胺的合成工艺改进[J].中国药物化学杂志,2017,27(1):43-45.