PROCESS FOR THE PREPARATION OF THE ANGIOTENSIN II ANTAGONIST VALSARTAN

摘要

The present invention provides a method for the preparation of N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-valine (Valsartan) which comprises; treating N-[[2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methy]-L-valine methyl ester (X)with oxalic acid or its hydrates in a solvent to produce N-[[2'-(1-triphenylmethyl-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-tetrazol-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.