依托考昔杂质Ⅰ的合成工艺
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摘要
依托考昔是一种非甾体药,在动物模型中它具有抗炎、镇痛和解热作用。而在依托考昔的合成过程中会产生一系列的杂质,其中依托考昔杂质Ⅰ是最主要的杂质之一。为了更好地研究该物质并提高依托考昔的产率,本文开发了一条关于依托考昔杂质Ⅰ新的合成路线并对其进行了工艺优化,以5-氯-2-羟基吡啶为起始原料,经取代和Suzuki偶联等反应得到目标产物,该方法原料简单易得、反应条件温和、操作简单且收率较高,总收率为25.22%。
Etoricoxib belongs to a kind of nonsteroidal drug serving as anti-inflammatory,analgesic and antipyretic in animal model.A series of impurities will be produced among the synthesis process of etoricoxib,especially the etoposide impurity Ⅰ.A new synthetic route for etoposide impurity Ⅰ,in which the synthetic route was optimized,was developed to study the impurity and increase the yield of etoricoxib.The target product was synthesized by substitution and Suzuki coupling reaction with 5-chloro-2-hydroxypyridine as the starting material.It was easy to operate and control the reaction and the yield was higher in each step.The total yield was 25. 22%.
Etoricoxib belongs to a kind of nonsteroidal drug serving as anti-inflammatory,analgesic and antipyretic in animal model.A series of impurities will be produced among the synthesis process of etoricoxib,especially the etoposide impurity Ⅰ.A new synthetic route for etoposide impurity Ⅰ,in which the synthetic route was optimized,was developed to study the impurity and increase the yield of etoricoxib.The target product was synthesized by substitution and Suzuki coupling reaction with 5-chloro-2-hydroxypyridine as the starting material.It was easy to operate and control the reaction and the yield was higher in each step.The total yield was 25. 22%.
引文
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[5]Dinesh M,Archana S,Ranganathan R,et al.Bis azide–triphenylphosphine as a reagent for esterification at room temperature[J].Tetrahedron Lett,2015,56(50):6 975-6979.
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[10]Dutta U,Deb A,Lupton D W,et al.Cheminform abstract:the regioselective iodination of quinolines,quinolones,pyridones,pyridines and uracil[J].Cheminform,2015,51(100):17 744-17 747.
[11]Elliott R L,Ryther K B,Holladay M W,et al.Furopyridine,thienopyridine,pyrrolopyridine and related pyrimidine,pyridazine and triazine compounds useful in controlling chemical synaptic transmission[P]:WO:1997005139 A1,1997-02-13.
[12]Suzuki A.The Suzuki reaction with arylboron compounds in arene chemistry[J].Cheminform,2004,35(8):53-106.
[13]Suzuki A.The Suzuki reaction with arylboron compounds in arene chemistry[J].Cheminform,2004,35(8):53-106.
[2]高巧灵,庞清江.依托考昔治疗急性痛风140例的镇痛效果评价[J].中国药业,2013,22(10):33-34.
[3]Pye,P J,Rossen,K,Maliakal,A,et al.Process for making2-aryl-3-aryl-5-halo pyridines useful as COX-2 inhibitors[P].US:6127545,2000-10-03.
[4]泮海亚.依地昔布关键中间体的合成及表征[J].广州化工,2012,40(4):42-44.
[5]Dinesh M,Archana S,Ranganathan R,et al.Bis azide–triphenylphosphine as a reagent for esterification at room temperature[J].Tetrahedron Lett,2015,56(50):6 975-6979.
[6]Jin Li,Kevin K,C Liu.Syntheis approaches to the 2002new drugs.[J].Mini-Rev Med Chem,2004,4:207-233.
[7]Manimaran T,Impastato F J.Resolution of racemic[P].US:4968837,1990-11-06.
[8]Sleevi M.C,Maniaskinian G,Moses M.Subestituted 2-aminotetralins[P].US:5382596,1995-01-17.
[9]高文涛,孙连杰.碘代水杨醛合成方法的改进[J].化学研究与应用,2013,25(2):257-260.
[10]Dutta U,Deb A,Lupton D W,et al.Cheminform abstract:the regioselective iodination of quinolines,quinolones,pyridones,pyridines and uracil[J].Cheminform,2015,51(100):17 744-17 747.
[11]Elliott R L,Ryther K B,Holladay M W,et al.Furopyridine,thienopyridine,pyrrolopyridine and related pyrimidine,pyridazine and triazine compounds useful in controlling chemical synaptic transmission[P]:WO:1997005139 A1,1997-02-13.
[12]Suzuki A.The Suzuki reaction with arylboron compounds in arene chemistry[J].Cheminform,2004,35(8):53-106.
[13]Suzuki A.The Suzuki reaction with arylboron compounds in arene chemistry[J].Cheminform,2004,35(8):53-106.