N,N-Bis[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-L-valine methyl ester | 1353844-77-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N,N-Bis[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-L-valine methyl ester
• 英文别名: methyl (2S)-2-[bis[[4-(2-cyanophenyl)phenyl]methyl]amino]-3-methylbutanoate
• CAS: 1353844-77-5
• 化学式: C₃₄H₃₁N₃O₂
• 分子量: 513.6
• InChiKey: ACHVMIPEFRAHGY-XIFFEERXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  77.1
• 氢给体数：
  0
• 氢受体数：
  5

文献信息

• PROCESS FOR THE PREPARATION OF VALSARTAN
  申请人：Chinta Raveendra Reddy

  公开号：US20130144067A1

  公开（公告）日：2013-06-06

  The present invention relates to a process for the preparation of pure Valsartan (I) substantially free from impurities of formulae (Ia), (Ib), and (Ic), which comprises: (i) condensing 2-(4′-bromomethylphenyl)benzonitrile of formula (II) with L-valine methyl ester hydrochloride of formula (V) in the presence of a base in a solvent to produce N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester of formula (VI); (ii) treating the compound VI of step (i) with acid followed by treating with base to produce pure compound VI substantially free from dimeric impurity of formula (Via); (iii) reacting the pure compound of formula (VI) with n-valeryl chloride in the presence of a base to produce pure N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII) substantially free from alkene impurity of formula (Vila); (iv) reacting the compound of formula (VII) with trialkyltin chloride and a metal azide in a solvent at a reflux temperature to produce N-(1-oxopentyl)-N-[[2′-(2-tributyltinte-trazol-5-yl)-(1,1′-biphenyl)-4-yl]methyl]-(L)-valine methyl ester of formula (VHIb) free from thermal degradation impurity (Villa); (v) hydrolyzing the compound of formula (VHIb) in the presence of alkaline conditions to produce Valsartan (I).

  本发明涉及一种制备纯缬沙坦（I）的方法，该方法基本上不含有式（Ia）、（Ib）和（Ic）的杂质，包括：（i）在溶剂中，将式（II）的2-(4'-溴甲基苯基)苯甲腈与式（V）的L-缬氨酸甲酯盐酸盐在碱的存在下缩合，产生式（VI）的N-[(2'-氰基联苯基-4-基)甲基]-(L)-缬氨酸甲酯；（ii）用酸处理步骤（i）中的化合物VI，然后用碱处理，产生基本上不含有式（Via）的纯化合物VI；（iii）在碱的存在下，将式（VI）的纯化合物与正戊酰氯反应，产生基本上不含有式（Vila）的纯N-戊酰基-N-[(2'-氰基联苯基-4-基)甲基]-(L)-缬氨酸甲酯（VII）；（iv）将式（VII）的化合物与三烷基锡氯化物和金属偶氮化物在溶剂中在回流温度下反应，产生基本上不含有热降解杂质（Villa）的N-(1-氧代戊基)-N-[[2'-(2-三丁基锡-1H-1,2,3-三唑-5-基)-(1,1'-联苯基)-4-基]甲基]-(L)-缬氨酸甲酯（VHIb）；（v）在碱性条件下水解式（VHIb）的化合物，产生缬沙坦（I）。
• US8981109B2
  申请人：——

  公开号：US8981109B2

  公开（公告）日：2015-03-17