Zhejiang Tianyu Pharmaceutical Co., Ltd.

Yongjun Tu

Zhen Wang

Guorong Zhu

Gang Liu

Wei Xiao

Zuwei He

Shaojun Xu

Wenlong Xie

Dequan Su

Yi Zhang

Ruiyun Lv

Rongde Cheng

Lingchao Peng

Rongming Huang

Huilin Yang

Provided is a preparation method of losartan, which is prepared by reacting a cyano group-containing intermediate represented by formula (I) with an azide reagent in toluene in the presence of a catalyst; wherein, after the reaction is completed, azide ions are removed by means of the following process: adding water to divide the reaction system into three layers, separating the intermediate layer and adding n-butanol to the intermediate layer for dilution, and adding triphenylphosphine to the resulting diluted solution so as to remove residual azide ions from the diluted solution. The preparation method provided by the present invention does not need to use sodium nitrite, thus fundamentally eliminating the formation of genotoxic impurities nitrosamines. The resulting target product has good purity, high yield, a simple preparation process, mild and easy-to-control operating conditions, and good safety, and is suitable for large-scale industrial production,

Preparation method for losartan

The present invention discloses a method for preparing an anti-heart-failure medicine LCZ696. The preparing method comprises the following step (formula (I)): in an organic solvent, a Sacubitril dicyclohexylamine salt reacts with valsartan under the effect of a sodium hydroxide aqueous solution, and the anti-heart-failure medicine LCZ696 is obtained. The preparing method of the present invention is simple in process and omits the procedures of ion exchange from a sodium salt to a calcium salt and hydrochloric acid dissociation in an existing production process, residues of calcium ions are avoided, and the production efficiency is effectively improved.

Method for preparing anti-heart-failure medicine LCZ696

A method for preparing Aliskiren and intermediate thereof, which comprises the following steps: reacting 4-bromo-1-methoxy-2-(3-methoxypropoxy)benzene with magnesium isopropyl chloride and n-BuLi to obtain the compound of formula XXII; reacting the product of methylsulfonylation of the compound of formula XIX with anhydrous LiBr to obtain the compound of formula XXI; obtaining the intermediate of Aliskiren shown as formula XV by reacting the compound of formula XXII with the compound of formula XXI in an ether as the solvent and in the presence of a catalyst containing iron; then reacting the compound of formula XV with the compound of formula VII to obtain the compound of formula XXIII, following removing Rfrom the amino group and obtaining Aliskiren shown as formula I.

Method for preparing aliskiren and its intermediates thereof

Growing community of inventors

Zhejiang, China

Yongjun Tu