Preparation method of LZ969

Preparation method of LZ969

  • CN 105,001,173 A
  • Filed: 06/30/2015
  • Published: 10/28/2015
  • Est. Priority Date: 06/30/2015
  • Status: Active Application
First Claim
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1. the preparation method of a LZ969, it is characterized in that, described LZ969 is valsartan and the 4-(((2S of mol ratio 1:

  • 1,4R)-1-(1,1 '"'"'-biphenyl-4-base)-5-oxyethyl group-4-methyl-5-oxo-pentane-2-base) amino)-4-ketobutyric acid mixture, wherein the preparation method of valsartan comprises the following steps;

    Step a, the synthesis of Valine methyl esters, react under thionyl chloride and anhydrous methanol low temperature and generate protochloride sulfuric ester, in Valine, then add protochloride sulfuric ester carry out esterification, add re-crystallizing in ethyl acetate after reaction and obtain Valine methyl ester hydrochloride;

    Step b, in Valine methyl ester hydrochloride, add 2 '"'"'-cyano group-4-brooethyl-biphenyl take tetrahydrofuran (THF) as solvent, and nucleophilic substitution reaction under sodium carbonate exists, obtains N-[2 '"'"'-cyano group-(biphenyl-4-base)-methyl]-Valine methyl ester hydrochloride;

    Step c, to N-[2 '"'"'-cyano group-(biphenyl-4-base)-methyl] add valeryl chloride in-Valine methyl ester hydrochloride, take sodium carbonate as acid binding agent, acetone is solvent, is obtained by reacting N-[2 '"'"'-cyano group-(biphenyl-4-base)-methyl]-N-valeryl;

    Steps d, adds N-[2 '"'"'-cyano group-(biphenyl-4-base)-methyl in reaction vessel]-N-valeryl, sodiumazide, chloro tributyl tin, be solvent with pyridine, reacting by heating obtains valsartan.

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