149709-58-0

Usage

Uses

Used in Pharmaceutical Industry:
((R)-2-biphenyl-4-yl-1-forMylethyl)carbaMic acid t-butyl ester is used as an impurity in the development of LCZ696 (L270005), a novel dual-acting inhibitor of angiotensin II receptor and neprilysin. It plays a role in blood pressure reduction, which is essential for managing hypertension and related cardiovascular conditions.
The compound's involvement in the development of LCZ696 highlights its potential application in the pharmaceutical industry, particularly in the treatment of hypertension and other related conditions. Its presence as an impurity in the synthesis process may also warrant further investigation into its potential effects on the overall efficacy and safety of the drug.

Upstream product

• 1213855-60-7 methyl (R)-3-(4-bromophenyl)-2-((tert-butoxycarbonyl)amino)propanoate 
• 1426129-50-1 N-[(1R)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)ethyl]carbamic acid tert-butyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 62561-75-5 (R)-2-amino-3-(4-iodophenyl)propanoic acid 
• 673-06-3 D-(R)-phenylalanine 
• 1383027-39-1 C₁₇H₂₃F₃N₂O₇S 
• 929872-80-0 tert-butyl (R)-3-(4-hydroxyphenyl)-1-[methoxy(methyl)amino]-1-oxopropan-2-ylcarbamate 
• 70642-86-3 N-(tert-butoxycarbonyl)-D-tyrosine 
• 149709-56-8 methyl N-(tert-butoxycarbonyl)-O-[(trifluoromethyl)sulfonyl]-D-tyrosinate 
• 149818-98-4 methyl (R)-α-<<(1,1-dimethylethoxy)carbonyl>amino><1,1'-biphenyl>-4-propanoate 
• 76757-90-9 N-(tert-butoxycarbonyl)-D-tyrosine methyl ester 
• 128779-47-5 (2R)-3-(biphenyl-4-yl)-2-[(tert-butoxycarbonyl)amino]propanoic acid 
• 162972-36-3 (R)-α-<<(1,1-dimethylethoxy)carbonyl>amino>-N-methoxy-N-metyl<1,1'-biphenyl>-4-propanamide 

Downstream Products

• 149709-59-1 (R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpent-2-enoic acid ethyl ester 
• 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 
• 1012341-50-2 (2R,4S)-5-[(1,1‘-biphenyl)-4-yl]-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid 
• 149690-12-0 (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-amino-2-methylpentanoic acid ethyl ester hydrochloride 
• 149709-60-4 ethyl (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoate 
• 149709-59-1 ethyl 5-(4-<1,1'-biphenyl>yl)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-2-methyl-2-pentenoate 
• 149709-62-6 α-ethyl (αR,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 
• 149709-63-7 α-ethyl (γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 753421-85-1 ethyl (γS)-γ-amino-α-methyl<1,1'-biphenyl>-4-pentanoate 

Relevant academic research and scientific papers

Synthesis method of sacubitril drug intermediate

The invention relates to the technical field of synthesis of medical intermediates, in particular to a synthesis method of a sacubitril drug intermediate. The synthesis method comprises the followingsynthesis route: under the protection of nitrogen, adding a compound II and a solvent into a reaction flask, stirring to dissolve, adding diisobutylaluminum hydride according to the feeding molar ratio of compound II to diisobutylaluminum hydride (DIBAH) of 1: (1-2), and controlling the temperature, stirring for reaction, and monitoring the reaction by TLC; after the reaction is finished, adding aKHSO4/water solution for quenching reaction; combining the obtained solution with a 1N HCl solution, stirring for 5 minutes, and separating an organic phase; extracting the aqueous phase with EtOAc,combining the organic phases, drying with anhydrous sodium sulfate, and concentrating to dryness to obtain a compound I; according to the invention, diisobutylaluminum hydride is selected to replace lithium aluminum hydride which is easy to explosively decompose when encountering water. The method is simple in reaction operation, high in yield and suitable for industrial large-scale production.

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.

Preparation method of N-Boc biphenyl alaninal

The invention discloses a preparation method of N-Boc-biphenyl alaninal, and the preparation method comprises the following steps: the N-Boc-biphenyl alaninal can be obtained by oxidation reaction of N-Boc-biphenyl alaninol and 2-iodoxybenzoic acid in an organic solvent. The method has the advantages of simple operation, high yield, high purity, low cost and little pollution, and is suitable for industrial production.

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.

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.

Method for preparing Sacubitril intermediate of anti-heart-failure medicine

The invention discloses a method for preparing a Sacubitril intermediate of anti-heart-failure medicine as indicated in the formula (VII).The method comprises the following steps of taking D-phenylalanine which is low in price and easy to obtain as the raw material, and conducting an iodination reaction, an esterification reaction, a Boc protection reaction, a negishi coupling reaction, a DIBAL-H reduction reaction and a wittig reaction, so that the Sacubitril intermediate is obtained through preparation.The method for preparing the Sacubitril intermediate is mild in reaction condition and environmentally friendly, compared with existing preparation methods, the yield is higher, and the method is economical, effective and suitable for large-scale industrialized production.

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.

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: where R1-R6, a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.