149690-12-0Relevant articles and documents
Synthesis of a Precursor to Sacubitril Using Enabling Technologies
Lau, Shing-Hing,Bourne, Samuel L.,Martin, Benjamin,Schenkel, Berthold,Penn, Gerhard,Ley, Steven V.
, p. 5436 - 5439 (2015)
An efficient preparation of a precursor to the neprilysin inhibitor sacubitril is described. The convergent synthesis features a diastereoselective Reformatsky-type carbethoxyallylation and a rhodium-catalyzed stereoselective hydrogenation for installation of the two key stereocenters. Moreover, by integrating machine-assisted methods with batch processes, this procedure allows a safe and rapid production of the key intermediates which are promptly transformed to the target molecule (3·HCl) over 7 steps in 54% overall yield.
Application of Transition-Metal Catalysis, Biocatalysis, and Flow Chemistry as State-of-the-Art Technologies in the Synthesis of LCZ696
Gu, Xingxian,Zhao, Jibin,Chen, Like,Li, Yunzhong,Yu, Bo,Tian, Xiangguang,Min, Zhongcheng,Xu, Su,Gu, Huijuan,Sun, Junjie,Lu, Xiaoquan,Chang, Meng,Wang, Xufan,Zhao, Liqun,Ye, Shengqing,Yang, Hongwei,Tian, Yingtao,Gao, Feng,Gai, Yu,Jia, Guanghua,Wu, Jingjing,Wang, Yan,Zhang, Jianghua,Zhang, Xuesong,Liu, Weichun,Gu, Xin,Luo, Xi,Dong, Hai,Wang, Huaimin,Schenkel, Berthold,Venturoni, Francesco,Filipponi, Paolo,Guelat, Bertrand,Allmendinger, Thomas,Wietfeld, Bernhard,Hoehn, Pascale,Kovacic, Nikola,Hermann, Luca,Schlama, Thierry,Ruch, Thomas,Derrien, Nadine,Piechon, Philippe,Kleinbeck, Florian
, p. 6844 - 6853 (2020/06/04)
LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in a single chemical compound. While valsartan is an established drug substance, a new manufacturing process suitable for large-scale commercial production had to be developed for sacubitril. The use of chemocatalysis, biocatalysis, and flow chemistry as state-of-the-art technologies allowed to efficiently build up the structure of sacubitril and achieve the defined performance targets.
Purification method of sacubitril valsartan sodium intermediate
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Paragraph 0053-0119, (2020/03/09)
The invention discloses a purification method of a sacubitril valsartan sodium intermediate. According to the method, a certain amount of specific lower fatty acid ester and a low-polarity solvent areadopted; the method comprises the following steps: recrystallizing and purifying an intermediate 1: ((2R, 4S)-4-amino-5-biphenyl-4-yl-2-methyl ethyl valerate hydrochloride) crude product prepared from a thionyl chloride/ethanol system, and removing acidic substances in the crude product. The method has characteristics of simple operation; corrosion on instrument equipment due to the use of the n-heptane repeated reduced pressure concentration method in the prior art is avoided, and the yield of the intermediate 1 is increased obviously. The purification method provided by the invention is more beneficial to subsequent preparation of sacubitril valsartan sodium, and is suitable for large-scale industrial production.