一种西他列汀关键中间体的合成方法_缪炳林.pdfVIP

一种西他列汀关键中间体的合成方法_缪炳林.pdf

工艺管控

一种西他列汀关键中间体的合成方法

缪炳林，周魏魏，关健，李延洁*

(台州达辰药业有限公司，浙江临海317000)

摘要：文章报道了一种制备西他列汀关键中间体—吡嗪盐酸盐(VI)的方法。该方法以三氟乙酸乙酯(I)为起始原料，

经水合肼取代，氯乙酰氯缩合，得到中间体(II)。之后通过三氯氧磷脱水环化得到中间体(III)，然后其通过碘代，得到新

化合物(IV)(2-碘甲基-5-三氟甲基-1,3,4-噁二唑)。通过核磁和液质表征，鉴别了该化合物(IV)的结构。中间体(IV)被

乙二胺取代得到中间体(V)，最后经盐酸环化成盐得到产物吡嗪盐酸盐(VI)。反应总收率可达67%，纯度99%。

关键词：西他列汀；吡嗪盐酸盐；2-碘甲基-5-三氟甲基-1,3,4-噁二唑；碘代；合成

中图分类号：TQ46 文献标志码：A文章编号：1008-4800(2025)31-0138-04

DOI:10.19900/ki.ISSN1008-4800.2025.31.035

Asyntheticmethodforkeyintermediateofsitagliptin

MIAOBinglin,ZHOUWeiwei,GUANJian,LIYanjie*

(TaizhouDachenPharmaceuticalCo.,Ltd.,Linhai317000,China)

Abstract:Asyntheticmethodforpreparingthekeyintermediateofsitagliptin-pyrazinehydrochloride(VI)wasreported.Inthis

process,ethyltri■uoroacetate(I)wasusedasthestartingmaterial,theintermediate(II)wasobtainedfromsubstitutionofhydrazine

hydrateandcondensationofchloroacetylchloride.Then,theintermediate(III)wasaffordedfromthedehydrationandcyclization

ofintermediate(II)byusingphosphorusoxychloride.Afteriodinationofintermediate(III),thenewcompound(IV)(2-iodimethyl-

5-trifluoromethyl-1,3,4-oxadiazole)wassynthesized.Thestructureofcompound(IV)wascharacterizedandidentif iedby

nuclearmagneticresonanceandliquidchromatography-massspectrometry.Next,fromthesubstitutionoftheintermediate

(IV)byusingethylenediamine,theintermediate(V)wasafforded.Finally,afterthecyclizationofintermediate(V),theproduct

pyrazinehydrochloride(VI)wasobtainedbyusinghydrochloricacid.Thetotalyieldofthisprocesscouldreach67%andthe

puritycouldreach99%.

Keywords:sitagliptin;pyrazinehydrochloride;2-iodomethyl-5-tri■uoromethyl-1,3,4-oxadiazole;iodization;synthesis