149709-59-1

Basic information

• Product Name: (R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoate
• Synonyms: (R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoate;(4R)-5-[1,1'-Biphenyl]-4-yl-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-methyl-2-pentenoic acid ethyl ester;(R)-Ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpent-2-enoate;2-Pentenoic acid, 5-[1,1'-biphenyl]-4-yl-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-methyl-, ethyl ester, (4R)-;Ethyl 5-(4-[1,1'-biphenyl]yl)-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-methyl-2-pentenoate
• CAS NO: 149709-59-1
• Molecular Formula: C₂₅H₃₁NO₄
• Molecular Weight: 409.51794
• EINECS: -0
• Product Categories: LCZ696
• Mol File: 149709-59-1.mol

Chemical Properties

• Boiling Point: 562.7±50.0 °C(Predicted)
• Appearance: /
• Density: 1.081±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 11.14±0.46(Predicted)
• CAS DataBase Reference: (R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoate(CAS DataBase Reference)
• NIST Chemistry Reference: (R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoate(149709-59-1)
• EPA Substance Registry System: (R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoate(149709-59-1)

Safety Data

• Hazardous Substances Data: 149709-59-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpent-2-enoate is used as a potential pharmaceutical compound for its unique structural features. The presence of the biphenyl and tert-butoxycarbonyl amino groups may contribute to its interaction with biological targets, making it a candidate for the development of new drugs.
Used in Agrochemical Industry:
In the agrochemical industry, (R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpent-2-enoate may be utilized as a precursor or intermediate in the synthesis of agrochemicals. Its complex structure could provide novel properties for the development of new pesticides or other agricultural chemicals.
Used in Chemical Research:
(R,E)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpent-2-enoate is used as a subject of chemical research to explore its reactivity, stability, and potential applications in various chemical processes. Understanding its properties can lead to the discovery of new synthetic routes or the development of innovative materials.

Upstream product

• 149709-58-0 (R)-α-<<(1,1-dimethylethoxy)carbonyl>amino><1,1'-biphenyl>-4-propanal 
• 21382-82-1 (carbethoxyethylidene)triphenylphosphorane 
• 1426129-50-1 N-[(1R)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)ethyl]carbamic acid tert-butyl ester 
• 108-21-4 Isopropyl acetate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 162972-36-3 (R)-α-<<(1,1-dimethylethoxy)carbonyl>amino>-N-methoxy-N-metyl<1,1'-biphenyl>-4-propanamide 
• 128779-47-5 (2R)-3-(biphenyl-4-yl)-2-[(tert-butoxycarbonyl)amino]propanoic acid 
• 149818-98-4 methyl (R)-α-<<(1,1-dimethylethoxy)carbonyl>amino><1,1'-biphenyl>-4-propanoate 
• 1213855-60-7 methyl (R)-3-(4-bromophenyl)-2-((tert-butoxycarbonyl)amino)propanoate 
• 3728-20-9 D-tyrosine methylester hydrochloride 
• 60-18-4 L-tyrosine 
• 149709-56-8 methyl N-(tert-butoxycarbonyl)-O-[(trifluoromethyl)sulfonyl]-D-tyrosinate 
• 76757-90-9 N-(tert-butoxycarbonyl)-D-tyrosine methyl ester 

Downstream Products

• 753421-85-1 ethyl (γS)-γ-amino-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 149709-63-7 α-ethyl (γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 149709-63-7 α-ethyl (αS,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 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 
• 1012341-50-2 (2R,4S)-5-[(1,1‘-biphenyl)-4-yl]-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid 
• 752174-62-2 (2R,4S)-4-amino-5-biphenyl-4-yl-2-methylpentanoic acid ethyl ester 
• 1012341-48-8 (2E,4R)-5-{[1,1'-biphenyl]-4-yl}-4-{[(tert-butoxy)carbonyl]amino}-2-methylpent-2-enoic acid 

Relevant articles and documents

Method for synthesizing AHU377 calcium salt

The invention discloses a method for synthesizing an AHU377 calcium salt. The method comprises the following steps: reacting 4-bromo-D-phenylalanine with thionyl chloride, reacting obtained methyl 4-bromo-D-phenylalaninate hydrochloride with BOC acid anhydride, reacting the obtained reaction product with phenylmagnesium bromide to obtain N-tert-butyloxycarbonyl-amino-4,4-biphenyl-R-alanine methylester, reacting the N-tert-butyloxycarbonyl-amino-4,4-biphenyl-R-alanine methyl ester with sodium borohydride, reacting the obtained reaction product with ethyl 2-(triphenylphosphoranylidene)propionate to obtain ethyl (4R)-5-[1,1'-biphenyl]-4-yl-4-[[tert-butoxycarbonyl]amino]-2-methyl-2-pentenoate, reacting the ethyl (4R)-5-[1,1'-biphenyl]-4-yl-4-[[tert-butoxycarbonyl]amino]-2-methyl-2-pentenoatewith lithium hydroxide, performing catalytic hydrogenation, reacting the obtained catalytic hydrogenation product with thionyl chloride to obtain ethyl (2R, 4S)-5- ([1,1-biphenyl)-4-amino-2-methylpentenoate hydrochloride, and stirring and reacting the ethyl (2R, 4S)-5- ([1,1-biphenyl)-4-amino-2-methylpentenoate hydrochloride, calcium chloride and succinic anhydride to obtain the target product.The method has the advantages of simple steps, mild reaction conditions, high purity and high yield.

Method for preparing LCZ-696 key intermediate

The invention relates to a method for preparing an LCZ-696 key intermediate, and aims to provide a novel method for preparing the LCZ-696 key intermediate. The LCZ-696 key intermediate has high yield, high impurity and low requirement for production equipment and is easy for industrialized production. The method includes the following steps: 1, adding NaHCO3 in water, conducting stirring and dissolving until the obtained aqueous solution is clarified, cooling the NaHCO3 aqueous solution to 10-20 DEG C, maintaining the temperature constant, and dropwise adding a NaClO solution to the NaHCO3 aqueous solution; 2, adding isopropyl acetate, a compound I and NaBr successively into a reaction kettle, conducting stirring at 20-35 DEG C for 20-40min for sufficiently dissolving, and adding TEMPO; 3, rapidly and dropwise adding the NaHCO3-NaClO aqueous solution in the compound I-NaBr-TEMPO isopropyl acetate solution obtained in step 2, purifying a compound II, and then preparing a compound IV. The method has the advantages that the yield of the compound IV is increased to 80% or above from about 50% in the prior art, the content of impurities is reduced, the purity of the prepared product reaches 99.0% or above, and thus the prepared product can be directly used in a following reaction without being purified. Moreover, the reaction temperature can be controlled in the range of 10 to 35 DEG C, the requirements for industrial equipment and operation time are reduced, and industrial production is thus greatly facilitated.

Preparation method of sacubitril intermediate having low triphenylphosphine oxide content

The invention relates to a preparation method of a sacubitril intermediate having low triphenylphosphine oxide content. The preparation method comprises that water, isopropyl acetate, sodium bromide, sodium bicarbonate and tetramethylpiperidine oxide into (R)-tert-butyl(1-([1, 1'-biphenyl]-4-yl)-3-hydroxypropane-2-yl)carbamate, adding a sodium hypochlorite solution into the mixture drop by drop for a reaction, after the reaction, carrying out layering, taking an organic layer, adding ethoxyformylethylidenetriphenyl phosphorane into the organic layer, after a reaction, concentrating the reaction product, removing isopropyl acetate, adding ethanol, water and lithium hydroxide into the mixture, carrying out heating until reflux, carrying out concentration until drying, adding water and activated carclazyte into the product, carrying out stirring at the room temperature, filtering the mixture, adding ethanol and acetic acid into the filtrate, carrying out heating until reflux, and carrying out cooling and stirring to precipitate solids which are the sacubitril intermediate finished products. The preparation method can reduce triphenylphosphine oxide content of the (R)-tert-butyl(1-([1, 1'-biphenyl]-4-yl)-3-hydroxypropane-2-yl)carbamate.

Preparation method and application of high-optical-purity biphenylalanine and derivative thereof

The invention relates to a preparation method and application of high-optical-purity biphenylalanine and a derivative thereof. The preparation method employs an acidic resolution reagent and controls the pH value of a reaction so as to prepare a target compound. According to the invention, raw materials are simple, easily available and cheap; the product obtained after resolution has high optical purity, so the problem of a final product with high optical purity is hard to prepare through refining in the prior art; and the preparation method is simple to operate, high in security, and low in the usage amount of wastewater and energy consumption, can overcome EHS problems in drug development, and is suitable for industrial large-scale production.

Preparation method for gamma-aminovalerate derivatives

The invention discloses a preparation method for gamma-aminovalerate derivatives. The method comprises the steps of reduction, oxidization, Wittig reaction and hydrogenation reduction with a starting material of N-((tert-butoxycarbonyl)amino-4,4-biphenyl-R-propanoate. The method has the advantages that the process route is short; chiral impurities are reduced by fixing a chiral center in the raw material; oxidized impurities are prevented from being generated by protecting the primary amine; and by using a palladium-charcoal or ruthenium catalyst for assisting a ligand to reduce ethylenic bond, the chiral selectivity is high, the yield is high and the method is suitable for large-scale industrial production.

NOVEL PRODRUGS AND COMBINATIONS FOR TREATMENT OF HYPERTENSION AND CARDIOVASCULAR DISEASES

The invention relates a pharmaceutical composition comprising (i) prodrugs of NEP inhibitors, (ii) mutual prodrugs of angiotensin receptor antagonist and a NEP inhibitor, (iii) a combination of an angiotensin receptor antagonist prodrug and a NEP inhibitor and (iv) a combination of angiotensin receptor antagonist including prodrug, a NEP inhibitor prodrug and a diuretic drug (v) a combination of angiotensin receptor antagonist, a NEP inhibitor prodrug and a calcium channel blocker. The angiotensin receptor antagonist is selected from the group selected from the group consisting of allisartan, elisartan, candesartan, eprosartan, irbesartan, losartan, saprisartan, tasosartan, telmisartan and valsartan. The invention also includes a method for treating hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke.

NEW PROCESS

Provided is a new enantioselective process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ -amino- δ -biphenyl- a -methylalkanoic acid, or acid ester, backbone.

Dicarboxylic Acid Dipeptide Neutral Endopeptidase Inhibitors

The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described.In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50 = 5.0 nM) in vitro and in vivo.Blood levels of 21a were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys.Free drug concentrations were 10-1500 times greater than the inhibitory constant for NEP over the course of a 6 h experiment.A good correlation of free drug concentrations was obtained when comparing values determined by the ex vivo analysis to those calculated from direct HPLC measurements.Plasma atrial natriuretic factor (exogenous) levels were elevated in rats and dogs after oral administration of 19a.Urinary volume and urinary sodium excretion were also potentiated in anesthetized dogs treated with 21a.