1426129-50-1

Basic information

• Product Name: LCZ696 InteMediate
• Synonyms: LCZ696 InteMediate;(R)-tert-butyl (1-([1,1'-biphenyl]-4-yl)-3-hydroxypropan-2-yl)carbaMate;N-[(1R)-2-[1,1'-Biphenyl]-4-yl-1-(hydroxymethyl)ethyl]carbamic acid 1,1-dimethylethyl ester;tert-butyl (R)-(1-([1,1'-biphenyl]-4-yl)-3-hydroxypropan-2-yl)carbamate;1)(R)-tert-butyl (1-([1,1'-biphenyl]-4-yl)-3-hydroxypropan-2-yl)carbamate;LCZ-696 Intermediate 39;EOS-61581;Carbamic acid, N-[(1R)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)ethyl]-, 1,1-dimethylethyl ester
• CAS NO: 1426129-50-1
• Molecular Formula: C₂₀H₂₅NO₃
• Molecular Weight: 327.4174
• EINECS: -0
• Product Categories: LCZ 696;LCZ696
• Mol File: 1426129-50-1.mol

Chemical Properties

• Boiling Point: 514.5±50.0 °C(Predicted)
• Appearance: /
• Density: 1.103±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 11.85±0.46(Predicted)
• CAS DataBase Reference: LCZ696 InteMediate(CAS DataBase Reference)
• NIST Chemistry Reference: LCZ696 InteMediate(1426129-50-1)
• EPA Substance Registry System: LCZ696 InteMediate(1426129-50-1)

Safety Data

• Hazardous Substances Data: 1426129-50-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
LCZ696 InteMediate is used as a key intermediate for the preparation of Sacubitril (S080900) and Valsartan (V095750). These drugs are known for their therapeutic effects in treating heart failure and hypertension, respectively. The intermediate plays a vital role in the synthesis process, ensuring the development of effective and safe medications for patients.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 1426129-51-2 C₂₂H₂₃NO 
• 1573000-31-3 (S)-1-([1,1‘-biphenyl]-4-yl)-3-tert-butoxypropan-2-ol 
• 1573000-36-8 (1-([1,1‘-biphenyl]-4-yl)-3-chloropropan-2-yl)pyrrolidine-2,5-dione 
• 1573000-33-5 (R)-3-([1,1’-biphenyl]-4-yl)-2-aminopropan-1-ol hydrochloride 
• 1573000-38-0 (R)-1-(1-([1,1’-biphenyl]-4-yl)-3-tert-butoxypropan-2-yl)pyrrolidine-2,5-dione 
• 1573000-40-4 (R)-3-([1,1‘-biphenyl]-4-yl)-2-phthaloyl-chloropropan 
• 1573000-43-7 (R)-3-([1,1‘-biphenyl]-4-yl)-2-phthaloyl-tert-butoxypropane 
• 92-66-0 4-bromo-1,1'-biphenyl 
• 1573000-28-8 (S)-1-([1,1’-biphenyl]-4-yl)-3-chloropropan-2-ol 
• 1057002-37-5 4-[1-biphenyl-4-yl-meth-(Z)-ylidene]-2-phenyl-4H-oxazol-5-one 
• 1446104-51-3 (R)-2-benzoylamino-3-biphenyl-4-yl-propionic acid methyl ester 
• 4530-20-5 BOC-glycine 
• 128779-47-5 (2R)-3-(biphenyl-4-yl)-2-[(tert-butoxycarbonyl)amino]propanoic acid 

Downstream Products

• 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 
• 149709-60-4 ethyl (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoate 
• 1012341-50-2 (2R,4S)-5-[(1,1‘-biphenyl)-4-yl]-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid 
• 304-91-6 o-iodosobenzoic acid 
• 1012341-48-8 (2E,4R)-5-{[1,1'-biphenyl]-4-yl}-4-{[(tert-butoxy)carbonyl]amino}-2-methylpent-2-enoic acid 
• 149709-59-1 ethyl 5-(4-<1,1'-biphenyl>yl)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-2-methyl-2-pentenoate 

Relevant articles and documents

Sacubitril intermediate as well as synthesis method and application thereof

The invention belongs to the technical field of medicine, and particularly relates to a sacubitril intermediate and a synthetic method and application thereof, wherein the synthetic method comprises the steps: taking D-biphenyl alanine as an initial raw material, and successively carrying out multiple reactions; and crystallizing and filtering to obtain (R)-2-(N-tert-butyloxycarbonylamino)biphenylpropanol. According to the sacubitril intermediate and the synthetic method and application thereof disclosed by the invention, D-biphenyl alanine is selected as an initial raw material; the subsequent added reactants are combined for successive reaction for multiple times; and finally, (R)-2-(N-tert-butyloxycarbonylamino)biphenyl propanol is synthesized. The reaction steps are simple and environment-friendly; industrial production is facilitated, particularly, the chemical purity of the product can reach 96% or above; the yield can reach 85% or above, and good industrial prospects are achieved; in addition, according to the synthetic method of (R)-2-(N-tert-butyloxycarbonylamino)biphenyl propanol, the recycled metal catalyst and concentrated filtrate can be recycled, the synthesis cost of (R)-2-(N-tert-butyloxycarbonylamino)biphenyl propanol is low, and industrial production is better facilitated.

Preparation method of Sacubitril intermediate

The invention discloses a preparation method of an intermediate compound (R)-tert-butyl (1-((1,1'-diphenyl)-4-yl)-3-hydroxypropane-2-yl) carbamate. The preparation method is represented as the formulashown in the description. According to the preparation method, the steps are simple and short, the reaction yield is increased, reaction conditions are mild, most of the intermediates obtained in thereaction process are not required to be purified and can be subjected to the next reaction directly, large-batch synthesis is facilitated, chiral amine with stereospecificity is efficiently synthesized with aminotransferase, and the preparation method is more suitable for industrial production.

Preparation method of Sacubitril key intermediate

The invention discloses a synthesis and preparation method of Sacubitril key intermediate N-[(1R)-2-(1,1'-biphenyl)-4-yl-1-(hydroxymethyl)ethyl]carbamic acid tert-butyl ester. The preparation method comprises the steps of adopting 4-biphenylcarboxaldehyde and hydantoin as starting materials; carrying out condensation and hydrolysis 'one-pot method' reaction, esterification reaction, dissymmetricaltransamination reaction, and Boc protection and reduction reaction to synthesize and prepare the target product. The preparation method has the characteristics of easiness in obtaining the reaction raw materials, short path, high reaction stereoselectivity, mild conditions, simple and convenient process operation, and the like, and is suitable for industrial production.

NEW PROCESS FOR EARLY SACUBITRIL INTERMEDIATES

The invention relates to 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-α-methylalkanoic acid, or acid ester, backbone.

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.

Synthesis method of LCZ696 midbody

The invention discloses a synthesis method of an LCZ696 midbody (R)-tertiary butyl (1-([1,1'-biphenyl]-4-base)-3-hydroxyl propane-2-base) carbamic acid ester. The preparation method comprises the following steps that (1) a raw material BOC-D-tyrosine I reacts with substituent sulfonyl chloride to obtain a midbody II; (2) the midbody II and a phenyl Grignard reagent are subjected to coupling to obtain a midbody III; and (3) the midbody III is reduced through potassium borohydride to obtain (R)-tertiary butyl (1-([1,1'-biphenyl]-4-base)-3-hydroxyl propane-2-base) carbamic acid ester IV. The synthesis method utilizes cheap n-tosyl-l-alanyloxyindole to replace expensive and virulent trifluoromethanesulfonic acid, and meanwhile avoids to use the expensive metal catalyst Pd, the experiment is easy to operate, the yield is high, and the LCZ696 midbody is suitable for large-scale production.

R - biphenyl c serinol preparation method (by machine translation)

The invention relates to a preparation method for the intermediate sha kubi tune, in particular to a R - biphenyl c serinol preparation method, steps are as follows: first of all in order to D - tyrosine derivatives as raw materials with different substituted base sulfonic acid chloride (or anhydride) reaction, a compound represented by formula III, the compounds of the formula III are prepared through two routes the third ammonia is mellow R - biphenyl. Route a: type III of a compound represented by formula II shown in the reduction of the compound, then obtained by coupling the third ammonia is mellow R - biphenyl; line II: type III as shown in the coupling shown in formula V compound, further reduction to obtain R - biphenyl the third ammonia is mellow. Prepared by the method of the aforesaid compound R - biphenyl c sphingosine is model antihypertensive medicine LCZ696 (Entresto) of pegvisomant Sacubitril (AHU - 377) key intermediate. The method is simple in operation, short route, is suitable for industrial production. (by machine translation)

Preparation method of entresto key intermediate

The invention relates to the technical field of medicines and particularly relates to a preparation method of a novel entresto key intermediate. When the method provided by the invention is used for preparing the entresto key intermediate, the method is mild in reaction conditions and is green and environmentally friendly; meanwhile, the yield of the method is higher than that of the existing preparation method; the method is economical and effective and is suitable for large-scale industrial production.

PROCESS FOR PREPARATION OF SACUBUTRIL INTERMEDIATE

The present application relates to a process for preparation of tert-butyl (R)-(1-([1,1'-biphenyl]-4- yl)-3-hydroxypropan-2-yl)carbamate (IA). The compound of formula (IA) may be used as an intermediate for the preparation of sacubitril.

Preparation method of sacubitril intermediate

The invention discloses a synthesis method of a sacubitril intermediate and belongs to the field of chemical pharmacy. The method comprises the following steps: enabling reaction of a starting materials glycine and di-tert-butyl dicarbonate ester under an alkaline condition, and performing dehydrogenation and amino protection, performing substitution, deprotection and salification on a compound of a formula II by a 'one-pot method' and under the action of a chiral catalyst to obtain a compound of a formula III and with a chiral intermediate; and reducing the compound of the formula III, refining and salifying to obtain a compound of a formula IV, and performing amino protection on the compound of the formula IV and di-tert-butyl dicarbonate ester to generate a target product of a formula I, namely (R)-tertiary butyl (1-([1,1'-biphenyl]-4-yl)-3-hydroxyl propane-2-yl)carbamic acid ester. According to the synthesis method of the sacubitril intermediate, provided by the invention, the required raw materials and reagents are easily available, the reaction condition is mild, the total yield is high, the cost is low, two-time salification is a refining process, the aftertreatment is simple in operation, the product quality is reliable and stable, and the whole process is very suitable for industrialized production.