CAJ | 학술논문

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，6aS）－6－氨基－2，2－二甲基四氢－3aH－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1 H 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。
목적：고효합성항응혈약체격서락。방법4，6－이록－2－（병류기）－5－초기밀정재철분、을산작용하환원후여2－（（（3aR，4S，6R，6aS）－6－안기－2，2－이갑기사경－3aH－배무〔d〕〔1，3〕이양잡－4－기）양기）을순경C－N우련、중담화성배，재여（1R，2R）－2－（3，4－이불분기）배병알친핵취대，최후산해탈병차기보호득도체격서락。결과여결론목표화합물적총수솔약위55％，결구경1 H NMR화 MS학증。해합성로선반응보취소，조작간편，반응조건온화，수솔고，괄합공업화생산。
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.