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    • 23. 发明授权
    • Process for the preparation of angiotensin II antagonist
    • 制备血管紧张素II拮抗剂的方法
    • US07880015B2
    • 2011-02-01
    • US12309016
    • 2007-06-29
    • Sankar Reddy BudidetSenthil Kumar NatarajanVenkata Kishore GowrabathinaRamesh DandalaSivakumaran Meenakshisunderam
    • Sankar Reddy BudidetSenthil Kumar NatarajanVenkata Kishore GowrabathinaRamesh DandalaSivakumaran Meenakshisunderam
    • C07D257/04
    • C07D257/04
    • The present invention provides a method for the preparation of N-(1-oxopentyl)-N-[[2′-(1H-tetra-zol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-L-valine (Valsartan) which comprises; treating N-[[2′-(1-triphenylmethyl-tetra-zol-5-yl)biphenyl-4-yl]methyl]-L-valine methyl ester (X) with oxalic acid or its hydrates in a solvent to produce N-[[2′-(1-triph-enylmethyl-tetrazol-5-yl)biphenyl-4-yl]methy]-L-valine methyl ester oxalate (Xa) and treating the compound (Xa) with a base in a solvent followed by reacting with valeryl chloride in presence of base in a solvent to produce N-[[2′-(1-triphenylmethyl-tetra-zol-5-yl)[1,1′biphenyl]-4-yl]methyl]-N-valeryl-L-valine methyl ester (XI), de-protecting the compound (XI) using anhydrous acidic conditions to produce N-(1-oxopentyl)-N-[[2′-(1-H-tetrazol-5-yl)[1,1′biphenyl]-4-yl]methyl-L-valine methyl ester (V) followed by treating with base in a solvent to produce Valsartan.
    • 本发明提供了制备N-(1-氧代戊基)-N - [[2' - (1H-四唑-5-基)[1,1'-联苯] -4-基]甲基 ] -L-缬氨酸(缬沙坦),其包含 用草酸或其水合物在溶剂中处理N - [[2' - (1-三苯基甲基 - 四唑-5-基)联苯-4-基]甲基] -L-缬氨酸甲酯(X),产生N - [[2' - (1-三 - 辛基甲基 - 四唑-5-基)联苯-4-基]甲基] -L-缬氨酸甲酯草酸酯(Xa)并用碱在溶剂中处理化合物(Xa) 然后在碱存在下与戊酰氯在溶剂中反应,生成N - [[2' - (1-三苯基甲基 - 四唑-5-基)[1,1'-联苯] -4-基]甲基] N-缬氨酰-L-缬氨酸甲酯(XI),用无水酸性条件脱保护化合物(Ⅺ),得到N-(1-氧代戊基)-N - [[2' - (1-H-四唑-5 - 基)[1,1'-联苯] -4-基]甲基-L-缬氨酸甲酯(V),然后用溶剂中的碱处理,得到缬沙坦。