149709-60-4

Basic information

• Product Name: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpentanoate
• Synonyms: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpentanoate;Ethyl (2R,4S)-4-([1,1'-biphenyl]-4-ylmethyl)-4-[(tert-butoxycarbonyl)amino]-2-methylbutanoate;LCZ702;Ethyl (2R,4S)-5-(4-biphenylyl)-2-methyl-4-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)pentanoate
• CAS NO: 149709-60-4
• Molecular Formula: C₂₅H₃₃NO₄
• Molecular Weight: 411.53382
• EINECS: -0
• Product Categories: LCZ696
• Mol File: 149709-60-4.mol

Chemical Properties

• Boiling Point: 549.3±50.0 °C(Predicted)
• Appearance: /
• Density: 1.066±0.06 g/cm3(Predicted)
• PKA: 12.15±0.46(Predicted)
• CAS DataBase Reference: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpentanoate(CAS DataBase Reference)
• NIST Chemistry Reference: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpentanoate(149709-60-4)
• EPA Substance Registry System: (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpentanoate(149709-60-4)

Safety Data

• Hazardous Substances Data: 149709-60-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(2R,4S)-Ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoate is used as a building block for the synthesis of various pharmaceutical compounds. Its unique structure allows it to be a key component in the development of new drugs with specific therapeutic properties.
Used in Chemical Synthesis:
(2R,4S)-Ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoate is used as a synthetic intermediate for the creation of complex organic molecules. Its versatility in chemical reactions makes it a valuable asset in the synthesis of a wide range of compounds, including those with potential applications in various industries such as pharmaceuticals, materials science, and agrochemicals.
Used in the Synthesis of Sacubitri (S080900):
(2R,4S)-Ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoate is specifically used as a building block in the synthesis of Sacubitri (S080900), an antihypertensive drug. Its incorporation into the drug's structure contributes to its efficacy in treating high blood pressure and related cardiovascular conditions.

Upstream product

• 1012341-54-6 (2R/S,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid 
• 75-03-6 ethyl iodide 
• 1174131-30-6 (R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentandic acid ethyl ester 
• 1426129-50-1 N-[(1R)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)ethyl]carbamic acid tert-butyl ester 
• 149709-58-0 (R)-α-<<(1,1-dimethylethoxy)carbonyl>amino><1,1'-biphenyl>-4-propanal 
• 149709-59-1 (R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpent-2-enoic acid ethyl ester 
• 64-17-5 ethanol 
• 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 
• 1012341-50-2 (2R,4S)-5-[(1,1‘-biphenyl)-4-yl]-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid 

Downstream Products

• 149690-12-0 (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-amino-2-methylpentanoic acid ethyl ester hydrochloride 
• 149709-62-6 α-ethyl (αR,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 752174-62-2 (2R,4S)-4-amino-5-biphenyl-4-yl-2-methylpentanoic acid ethyl ester 
• 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 

Relevant articles and documents

Preparation method of sacubitril intermediate

The invention provides a preparation method of a sacubitril intermediate. According to the method, 2-bromopropionic acid is used as an initial raw material and reacts with three-level silicon halide under the catalytic action of metal to generate a silicon ylide reagent, compared with a phosphorus ylide reagent, the reaction condition is mild, a hydrogenation reduction reaction can be carried out without alkaline hydrolysis, and ethyl esterification of a SOCl2 catalytic compound III is not influenced. Meanwhile, intramolecular or intermolecular polymerization impurities formed by removal of N protecting groups during ethyl esterification of the compound III can be avoided. The method has the advantages of short preparation process route, low cost, easily available raw materials, high yield and high purity, and is suitable for industrial mass production.

PROCESS FOR THE PREPARATION OF SACUBITRIL OR SALTS THEREOF

The present invention provides processes for the preparation of sacubitril or salts thereof. The present invention further provides intermediates of Formula IV, V and VI and their use for the preparation of sacubitril or salts thereof.

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 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.

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 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.