1038924-76-3

Upstream product

• 109-72-8 n-butyllithium 
• 1038924-65-0 (S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethyl-propionyl)-pyrrolidin-2-one 
• 108-18-9 diisopropylamine 
• 74-88-4 methyl iodide 
• 1038924-70-7 (3R,5S)-5-({[1,1'-biphenyl]-4-yl}methyl)-3-methylpyrrolidin-2-one 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1174130-65-4 (R)-5-biphenyl-4-ylmethyl-3-[1-dimethylaminometh-(E/Z)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 1174130-72-3 (R)-5-biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butylester 
• 51693-17-5 (S)-toluene-4-sulfonic acid 5-oxo-pyrrolidin-2-ylmethyl ester 
• 135697-21-1 (S)-(1-tert-butoxycarbonyl-5-oxopyrrolidin-2-yl)-methyl-4-methylbenzenesulfonate 
• 3315-91-1 4-biphenylylmagnesium bromide 
• 5122-94-1 4-biphenylboronic acid 
• 17342-08-4 (S)-Pyroglutaminol 
• 171288-20-3 N-boc-(2S,4R)-4-methylpyroglutamic acid 

Downstream Products

• 1012341-50-2 (2R,4S)-5-[(1,1‘-biphenyl)-4-yl]-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid 
• 1012341-54-6 (2S,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid 
• 1038924-79-6 (3S,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 1361408-15-2 (R)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl ester 
• 149709-62-6 α-ethyl (αR,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 149709-60-4 ethyl (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoate 
• 149690-12-0 (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-amino-2-methylpentanoic acid ethyl ester hydrochloride 

Relevant academic research and scientific papers

Compound for preparing sacubitril and preparation method and applications thereof

The invention provides a compound for preparing sacubitril and a preparation method and applications thereof. The compound has structures represented by the formula I and the formula II. The compoundhas two chiral centers. When the compound is applied to prepare sacubitril, complicated low-yield-selectivity reactions for introducing chiral groups are avoided completely, the reaction efficiency isgreatly improved; and the reaction steps are shortened. The compound represented by the formula I and the formula II can be used to prepare a sacubitril intermediate namely (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-amino-2-ethyl methyl valerate. The preparation method only comprises several simple steps, does not contain any reaction for introducing chiral centers, has the advantages of short synthesisroute, low synthesis cost, and convenient operation, and is suitable for industrial production.

A 5 - biphenyl -4 - amino -2 - methyl valeric acid synthesis of intermediates method

The invention provides a synthesis method of a new compound (3) disclosed in the specification and a synthesis method for preparing a 5-biphenyl-4-amino-2-methylvaleric acid intermediate from the compound (3). The method has excellent selectivity, and generates few diastereoisomers in the reaction process. The generated diastereoisomers can be removed just by simple recrystallization. Thus, the method is suitable for industrial production.

Novel synthesis method of key component Sacubitril of novel anti-heart-failure drug

The invention discloses a novel synthesis method of key component Sacubitril of a novel anti-heart-failure drug. The method includes transforming a starting material compound 1 to a compound 2; coupling the compound 2 with (1'1)-4-biphenylmagnesium bromide to obtain a compound 3; subjecting the compound 3 to hydrolysis reaction by loading a Boc protecting group, and preparing a compound 5 by means of one-pot reaction; subjecting the compound 5 to Boc group removal and esterification reaction to obtain a compound 6, and reacting the compound 6 with succinic anhydride without separation to obtain a compound 7, namely Sacubitril, wherein the route is as following.

NEW PROCESS FOR THE PREPARATION OF INTERMEDIATES USEFUL FOR THE MANUFACTURE NEP INHIBITORS

The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising -amino- -biphenyl- -methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

NEW PROCESS FOR THE PREPARATION OF INTERMEDIATES USEFUL FOR THE MANUFACTURE NEP INHIBITORS

The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

NEW PROCESSES

The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.