(S)-3-methyl-2-{[2'-(1H-tetrazole-5-yl)-biphenyl-4-yl-methyl]-amino}-butyric acid methylester | 1111177-24-2

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-3-methyl-2-{[2'-(1H-tetrazole-5-yl)-biphenyl-4-yl-methyl]-amino}-butyric acid methylester
• 英文别名: (S)-3-methyl-2-{[2'-(1H-tetrazol-5-yl)-biphenyl-4-yl-methyl]-amino}-butyric acid methylester；N-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine methyl ester；N-[[2'-(2H-Tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-valine methyl ester；methyl (2S)-3-methyl-2-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methylamino]butanoate
• CAS: 1111177-24-2
• 化学式: C₂₀H₂₃N₅O₂
• 分子量: 365.435
• InChiKey: JZYFUDOOMLVEJE-SFHVURJKSA-N

物化性质

• 沸点：
  555.1±60.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  92.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  L-缬氨酸甲酯盐酸盐 、 草酸 、 N-(三苯基甲基)-5-(4'-溴甲基联苯-2-基)四氮唑 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙酸乙酯 为溶剂， 以76%的产率得到N-[[2'-(1-triphenylmethyltetrazol-5-yl)biphenyl-4-yl]methyl]valine methyl ester oxalate
  参考文献：
  名称：

  New and Improved Manufacturing Process for Valsartan

  摘要：

  A new and improved industrially viable manufacturing process for valsartan, an antihypertension drug, is described.

  DOI：

  10.1021/op9000912

文献信息

• METHOD FOR ISOLATING 5-SUBSTITUTED TETRAZOLES
  申请人：Welzig Stefan

  公开号：US20090203920A1

  公开（公告）日：2009-08-13

  The invention relates to a method for isolating 5-substituted tetrazoles of general formula (I) in which R represents a substituted biphenyl radical during which the ring closure, starting from a corresponding nitrile, is carried out in organic solvents while using alkali, alkaline-earth or organotin azides. The organic phases containing the nitrile and the tetrazol are firstly mixed with water while firstly forming three liquid phases, after which the aqueous phase containing the azide and the phase containing the nitrile are separated out, and the middle organic phase containing the tetrazol is subsequently processed. In the case of ester groups to be saponified, this phase is mixed with alkali lye, after which the organic phase is separated out and the aqueous phase is acidified or otherwise, this phase is immediately acidified and purified.

  该发明涉及一种用于分离5-取代四唑的方法，其通式为（I），其中R代表取代联苯基团，其过程中，从相应的腈开始进行环闭合，在有机溶剂中使用碱、碱土或有机锡叠氮化合物。首先将含有腈和四唑的有机相与水混合，首先形成三个液相，然后将含有叠氮化合物的水相和含有腈的相分离出来，随后处理含有四唑的中间有机相。对于要皂化的酯基团，将此相与碱液混合，然后分离出有机相，将水相酸化，或者立即酸化和纯化此相。
• A process for the synthesis of valsartan
  申请人：KRKA, D.D., Novo Mesto

  公开号：EP1661891A1

  公开（公告）日：2006-05-31

  This invention relates to an improved process for preparing a valsartan, or a pharmaceutically acceptable salt thereof, or pharmaceutical preparation containing either entity wherein a compound of formula (II) or a salt thereof, is reacted with valine or an ester or a salt thereof in a solvent selected from the group consisting of methylene chloride, chloroform, butyl chloride, isopropyl acetate and tert-butyl methyl ether to form a compound of formula (IV) which is then acylated to form a compound of formula (VI) wherein R is hydrogen, alkyl, alkenyl or benzyl; which is then deprotected to give valsartan, and may be converted to a pharmaceutically acceptable salt and/or a pharmaceutical formulation. The invention also covers intermediates of formula (IV) and (VI) wherein R=H.

  这项发明涉及一种改进的制备缬沙坦、其药用可接受盐或含有任一实体的制药制剂的过程，其中式（II）的化合物或其盐在甲烷氯化物、氯仿、丁基氯化物、丙酸异丙酯和叔丁基甲基醚等溶剂中与缬氨酸或其酯或盐反应，形成式（IV）的化合物，然后酰化形成式（VI）的化合物，其中R为氢、烷基、烯基或苄基；然后去保护得到缬沙坦，并可转化为药用可接受的盐和/或制药配方。该发明还涵盖了中间体式（IV）和（VI），其中R=H。
• A PROCESS FOR THE SYNTHESIS OF VALSARTAN
  申请人：KRKA, D.D., Novo Mesto

  公开号：EP1831186B1

  公开（公告）日：2010-07-28
• New and Improved Manufacturing Process for Valsartan
  作者：Senthil Kumar .N、Shankar B. Reddy、Brajesh Kumar Sinha、Kagga Mukkanti、Ramesh Dandala

  DOI：10.1021/op9000912

  日期：2009.11.20

  A new and improved industrially viable manufacturing process for valsartan, an antihypertension drug, is described.