摘要
目的高效合成抗凝血药替格瑞洛。方法 4,6-二氯-2-(丙硫基)-5-硝基嘧啶在铁粉、乙酸作用下还原后与2-(((3aR,4S,6R,6a S)-6-氨基-2,2-二甲基四氢-3a H-环戊〔d〕〔1,3〕二氧杂-4-基)氧基)乙醇经C-N偶联、重氮化成环,再与(1R,2R)-2-(3,4-二氟苯基)环丙胺亲核取代,最后酸解脱丙叉基保护得到替格瑞洛。结果与结论目标化合物的总收率约为55%,结构经1H NMR和MS确证。该合成路线反应步骤少,操作简便,反应条件温和,收率高,适合工业化生产。
OBJECTIVE To Develop a highly-efficient synthesis method for anticoagulant ti-cagrelor.METHODS 4,6-Dichloro-2-（propylthio）pyrimidin-5-aminewasreducedintoaminocompoundviairon powder and acetic acid,and after the C-N cross-coupling and diazotization into the ring with 2-（（（3aR,4S,6R, 6aS）-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta〔d〕〔1,3〕dioxol-4-yl） oxy） ethanol,which was followed by nu-cleophilic substitution with （1R,2R）-2-（3,4-difluoro） cyclopropanamine and isopropylidene deprotection to provide ticagrelor.RESULTS and CONCLUSION The target compound was obtained in about 55%overall yield,and the chemical structure was confirmed by 1H NMR and MS.The developed method has some advantages such as few reac-tion steps,ease operations,mild reaction conditions,high yield,and suitable for industrial production.
出处
《海峡药学》
2015年第4期249-251,共3页
Strait Pharmaceutical Journal
关键词
化学合成
替格瑞洛
抗凝血药
Chemical synthesis
Ticagrelor
Anticoagulant
