米拉贝隆有关物质的合成
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摘要
为加强对米拉贝隆原料药的质量控制,以硝基苯乙腈和扁桃酸为原料合成了米拉贝隆的8个有关物质A~H,所合成的化合物结构经~1H-NMR,~(13)C-NMR与MS谱确证,其纯度经HPLC法检测,表明有关物质A~H可作为米拉贝隆质量控制的杂质对照品.
To strengthen the quality control of mirabegron API,eight related substances of mirabegron were synthesized from nitrophenylacetonitrile and mandelic acid. The structures of impuritie A ~ H were confirmed by ~1H,~(13)C NMR and MS,and their purities were determined by HPLC analysis. The impurities synthesized could be used as the reference substances of the related substances in the quality control of mirabegron.
To strengthen the quality control of mirabegron API,eight related substances of mirabegron were synthesized from nitrophenylacetonitrile and mandelic acid. The structures of impuritie A ~ H were confirmed by ~1H,~(13)C NMR and MS,and their purities were determined by HPLC analysis. The impurities synthesized could be used as the reference substances of the related substances in the quality control of mirabegron.
引文
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[15]郑亚东,和龙,贾志丹,等.米拉贝隆和去羟基米拉贝隆的合成[J].山东化工,2016,45(1):3-5,9.
[2]KHULLAR V,AMARENCE G,ANGULO J C,et al.Efficacy and tolerability of mirabegron,aβ3-adrenoceptor agonist,in patients with overactive bladder:results from a randomised european-australian phase 3 trial[J].Eur Urol,2013,63(2):283-295.
[3]KRAUWINKEL W,DIJK J V,SCHADDELEE M,et al.Pharmacokinetic properties of mirabegron,aβ3-adrenoceptor agonist:results from two phase I,randomized,multiple-dose studies in healthy young and elderly men and women[J].Clin Ther,2012,34(10):2144-2160.
[4]国家食品药品监督管理总局.化学药物杂质研究的技术指导原则[Z].2005-03-18.
[5]MARUYAMA T,SUZUKI T,ONDA K,et al.Amide derivatives or salts thereof:US,6346532[P].2002-02-12.
[6]张华,李杨,陈仕杰,等.米拉贝隆的合成方法:CN,103896872[P].2014-07-02.
[7]岑均达,黄伟,李强.一种米拉贝隆及其中间体的制备方法:CN,103387500[P].2013-11-13.
[8]葛德培,吴其华.米拉贝隆的合成方法:CN,104230840[P].2014-12-24.
[9]KAWAZOE S,SAKAMOTO K,AWAMURA Y,et al.Alpha-form or beta-form crystal of acetanilide derivative:EP,1440969[P].2004-07-28.
[10]THIRUMALAI R S,ESWARAIAH S,RAGHURAM S.Process for the preparation of 2-(2-aminothiazol-4-yl)-N-[4-(2-{[(2R)-2-hydroxy-2-phenylethyl]amino}ethyl)phenyl]acetamide monohydrochloride,its intermediates and polymorph thereof:WO,2014132270[P].2014-09-04.
[11]LAL B,SHENOY G,DAVE R,et al.Novel process for preparation of mirabegron and its intermediate:WO,2015162536[P].2015-10-29.
[12]范文进,曾正英,吴之波,等.米拉贝隆合成工艺改进[J].精细化工中间体,2016,46(4):42-47.
[13]毛龙飞,苑李双,颜茗彦,等.米拉贝隆的合成研究[J].化学研究与应用,2016,28(4):521-524.
[14]章磊,谭支敏,焦慧荣,等.米拉贝隆有关物质的合成[J].中国医药工业杂志,2014,45(1):9-12.
[15]郑亚东,和龙,贾志丹,等.米拉贝隆和去羟基米拉贝隆的合成[J].山东化工,2016,45(1):3-5,9.