149690-12-0

Basic information

• Product Name: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate
• Synonyms: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate HCl;LCZ696 Intermediate2;LCZ698;[1,1'-Biphenyl]-4-pentanoic acid, γ-amino-α-methyl-, ethyl ester, hydrochloride (1:1), (αR,γS)-;(2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate;(2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate hydrochloride;(2R,4S)-4-Amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride;(2R,4S)-4-Amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride (1:1)
• CAS NO: 149690-12-0
• Molecular Formula: C₂₀H₂₅NO₂*ClH
• Molecular Weight: 347.87894
• EINECS: -0
• Product Categories: LCZ696
• Mol File: 149690-12-0.mol
• Article Data: 27

Chemical Properties

• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate(CAS DataBase Reference)
• NIST Chemistry Reference: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate(149690-12-0)
• EPA Substance Registry System: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate(149690-12-0)

Safety Data

• Hazardous Substances Data: 149690-12-0(Hazardous Substances Data)

Usage

Description

(2R,4S)-Ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate, also known as (2R,4S)-4-Amino-5-(biphenyl-4-yl)-2-methylpentanoic Acid Ethyl Ester Hydrochloride, is an organic compound with a complex molecular structure. It is characterized by its chiral centers at the 2R and 4S positions, which give it unique properties and reactivity. (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate is a key intermediate in the synthesis of various pharmaceuticals due to its versatile functional groups and structural features.

Uses

Used in Pharmaceutical Synthesis:
(2R,4S)-Ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate is used as a reagent in the synthesis of LCZ696, an angiotensin II receptor and neprilysin receptor dual inhibitor. (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate plays a crucial role in the development of novel cardiovascular drugs that can effectively manage hypertension and heart failure by targeting two distinct pathways simultaneously.
Used in the Preparation of Novel NEP Inhibitor Prodrugs:
In addition to its role in the synthesis of LCZ696, (2R,4S)-Ethyl 5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoate is also utilized as a reagent in the preparation of novel NEP (neutral endopeptidase) inhibitor prodrugs. These prodrugs are designed to treat hypertension and cardiovascular diseases by inhibiting the NEP enzyme, which is involved in the regulation of blood pressure and the breakdown of certain peptides.
Used in the Development of Antihypertensive Agents:
The compound is further employed in the development of antihypertensive agents, which are essential for managing high blood pressure. By targeting the angiotensin II receptor and neprilysin receptor, these agents can help regulate blood pressure and reduce the risk of cardiovascular events.

Upstream product

• 64-17-5 ethanol 
• 1038924-71-8 (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-amino-2-methylpentanoic acid hydrochloride 
• 1039307-95-3 (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-amino-2-methylpentanoic acid 
• 31603-77-7 4-biphenylacetonitrile 
• 5728-52-9 (4-biphenylyl)acetic acid 
• 1012341-48-8 (2E,4R)-5-{[1,1'-biphenyl]-4-yl}-4-{[(tert-butoxy)carbonyl]amino}-2-methylpent-2-enoic acid 
• 1038924-76-3 (3R,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 108-91-8 cyclohexylamine 
• 1038924-70-7 (3R,5S)-5-({[1,1'-biphenyl]-4-yl}methyl)-3-methylpyrrolidin-2-one 
• 149709-60-4 ethyl (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoate 
• 149709-68-2 (R)-5-(biphenyl-4-yl)-4-tert-butoxycarbonylamino-2-methylpent-2-enoic acid 
• 149709-59-1 (R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpent-2-enoic acid ethyl ester 
• 149709-58-0 (R)-α-<<(1,1-dimethylethoxy)carbonyl>amino><1,1'-biphenyl>-4-propanal 

Downstream Products

• 1038925-00-6 (3S,5S)-5-biphenyl-4-ylmethyl-3-methylpyrrolidin-2-one 
• 1038924-70-7 (3R,5S)-5-({[1,1'-biphenyl]-4-yl}methyl)-3-methylpyrrolidin-2-one 
• 149690-05-1 α-ethyl (αR,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate monosodium salt 
• 1257265-87-4 5-[((1S,3R)-1-biphenyl-4-ylmethyl-3-carboxybutylcarbamoyl)methyl]furan-2-carboxylic acid 
• 1257265-86-3 (2R,4S)-5-biphenyl-4-yl-4-[(5-carboxymethylfuran-2-carbonyl)amino]-2-methylpentanoic acid 
• 149709-62-6 α-ethyl (αR,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 1257265-53-4 (2S,4S)-5-biphenyl-4-yl-4-((S)-3-carboxy-3-cyclohexyl-propionylamino)-2-methyl-pentanoic acid 
• 1257266-44-6 (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxyoxazole-5-carboxamido)-2-methylpentanoate 
• 1257266-41-3 (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxythiazole-5-carboxamido)-2-methylpentanoate 
• 1257265-54-5 C₃₁H₄₁NO₅ 
• 1257265-94-3 6-((1S,3R)-1-biphenyl-4-ylmethyl-3-carboxy-butylcarbamoyl)-2-ethoxy-pyrimidine-4-carboxylic acid 
• 1257265-62-5 (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-methoxybenzoylamino)-2-methylpentanoic acid ethyl ester 
• 1257265-93-2 6-((1S,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-butylcarbamoyl)-2-hydroxy-pyrimidine-4-carboxylic acid 
• 1257266-04-8 (2R,4S)-5-biphenyl-4-yl-2-methyl-4-[(pyridazine-4-carbonyl)-amino]-pentanoic acid 

Relevant articles and documents

Synthesis of a Precursor to Sacubitril Using Enabling Technologies

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

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

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.