目的 合成西他列汀杂质A。方法 将2,4,5-三氟苯乙酸、米氏酸和3-三氟甲基-5,6,7,8-四氢-1,2,4-三唑[4,3-α]吡嗪盐酸盐以“一锅法”反应得到中间体1-{3-三氟甲基-5,6-二氢-1,2,4-三唑并[4,3-a]吡嗪-7(8H)-基}-4-(2,4,5-三氟苯基)-1,3-丁二酮,再经硼氢化钠还原得到西他列汀杂质A。 结果 目标化合物的结构经IR、MS和1H-NMR确证。结论 该方法未见文献报道,具有成本低、操作简单、反应温和、收率高等优点。
Abstract
OBJECTIVE To synthesize the impurity A of sitagliptin which is a highly selective DPP-4 inhibitor used for treatment of type 2 diabetes. METHODS 1-{3-Trifluoromethyl-5,6-dihydro-1,2,4-triazo[4,3-a]piperazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)butane-1,3-dione was prepared from 2,4,5-triflurophenylacetic acid, meldrum's acid and 3-trifluromethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine hydrochloride with one-pot reaction, followed by reduction with sodium borohydride to yield the impurity A of sitagliptin. RESULTS The structure of the impurity A of sitagliptin was characterized by IR, MS, and 1H-NMR. CONCLUSION The established synthetic route of the impurity A in this study has not been reported in the literature, and has the advantages of low-cost, easy operation, mild reaction, and high overall yield.
关键词
西他列汀 /
杂质 /
合成 /
表征
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Key words
sitagliptin /
impurity /
synthesis /
characterization
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中图分类号：
R97
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参考文献
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脚注
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基金
国家“重大新药创制”科技重大专项(2009ZX09301-012)
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