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sacubitril

sacubitril Structure
sacubitril structure
CAS No.
1038924-61-6
Chemical Name:
sacubitril
Synonyms
sacubitril;sacubitril ISO 9001：2015 REACH;(S)-5-[(biphenyl-4-yl)Methyl]pyrrolidin-2-one;(S)-5-([1,1'-biphenyl]-4-ylMethyl)pyrrolidin-2-one;2-Pyrrolidinone, 5-([1,1'-biphenyl]-4-ylmethyl)-, (5S)-
CBNumber:
CB62721013
Molecular Formula:
C17H17NO
Molecular Weight:
251.32
MDL Number:
MFCD26401537
MOL File:
1038924-61-6.mol
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sacubitril Properties

Boiling point 473.6±24.0 °C(Predicted)
Density 1.117±0.06 g/cm3(Predicted)
pka 16.31±0.40(Predicted)
FDA UNII 17ERJ0MKGI
NCI Drug Dictionary sacubitril

sacubitril price More Price(2)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Chemenu CM198982 (S)-5-([1,1''-biphenyl]-4-ylmethyl)pyrrolidin-2-one 95% 1038924-61-6 1g $435 2021-12-16 Buy
Crysdot CD11361443 (S)-5-([1,1'-Biphenyl]-4-ylmethyl)pyrrolidin-2-one 95+% 1038924-61-6 1g $460 2021-12-16 Buy
Product number Packaging Price Buy
CM198982 1g $435 Buy
CD11361443 1g $460 Buy

sacubitril Chemical Properties,Uses,Production

Description

Sacubitril is a neprilysin inhibitor prodrug developed by Novartis that was approved as part of an orally administered supramolecular sodium salt complex with the angiotensin receptor blocker (ARB) valsartan in the U.S. and EU in 2015. Sacubitril/valsartan (also known as LCZ-696) is a first-in-class dual angiotensin receptor blocker neprilysin inhibitor (ARNI) marketed for the treatment of chronic heart failure with reduced ejection fraction (HFrEF). It represents a novel mechanistic approach to targeting HFrEF and is the first pharmacologic agent approved for HFrEF since 2004. Sacubitril is metabolized by enzymatic conversion of the ethyl ester to the active diacid (LBQ-657, structure not disclosed), which inhibits neprilysin and prevents endogenous natriuretic peptide degradation. Neprilysin inhibitors like sacubitril are not effective as monotherapy and need to be combined with a reninangiotensin aldosterone system (RAAS) inhibitor such as valsartan. Notably, dual neprilysin and angiotensin-converting enzyme (ACE) inhibition, as in omapatrilat, was found to be associated with an increased risk of life-threatening angioedema due to increased bradykinin levels. In phase III clinical trials, sacubitril/ valsartan displayed a superior safety profile to enalapril, with a 20% decrease in heart failure hospitalizations or cardiovascular death and a 16% reduction in the risk of death from any cause. Sacubitril/valsartan is now recommended as the standard of care for HFrEF as an alternative to ACEs and ARBs.

Synthesis

Several routes to sacubitril, particularly to advanced intermediates, have been published in the primary and patent literature.23 They differ generally in their choice of chiral pool starting material and their approach to introduction of the second stereocenter. The industrial scale synthesis of intermediate 47 has been reported. Accordingly, addition of the cuprate of biaryl bromide 41 to (S)-epichlorohydrin 42 followed by subjection to HCl provided chloropropanol 43 in 92% yield and 99% ee. Next, a Mitsunobu reaction involving succinimide 44 followed by treatment with refluxing HCl and NaOH generated the corresponding aminoalcohol, which was isolated via crystallization as the HCl salt prior to Boc protection to give N-Boc aminoalcohol 45 in >99% ee. Alcohol 45 was then carried through a four-step process to give acid 47 in 75% yield, starting with oxidation of the alcohol to the corresponding aldehyde with TEMPO/NaOCl. The organic phase was carried forward directly into a Wittig reaction with ylide 46, generating an |á,|?-unsaturated ester which was hydrolyzed to acid 47 with LiOH in an ethanol/water mixture. Interestingly, a separate patent disclosed the stereoselective hydrogenation of the trisubstituted olefin 47, in which subjection of 47 to catalytic [Ru(p-cymene)I2]2 and chiral phosphine ligand Mandyphos SL-M004-1 (48) under 40 bar of hydrogen gas in warm ethanol delivered 49 in 99:1 dr before recrystallization.
Subsequently, activation of the acid as the acid halide through the use of thionyl chloride and ethanol not only reestablished the ethyl ester but removed the Boc group, revealing a primary amine which then reacted with succinic anhydride to ultimately deliver sacubitril (V). The freebase form of sacubitril does not readily crystallize; the isolation of a number of pharmaceutically acceptable salts of sacubitril via crystallization, most preferably the calcium salt 50 or sodium salts, have been reported.
Preparation of the sacubitril/valsartan supramolecular complex (trisodium salt, hemihydrate) has been described on a kilo-scale from sacubitril calcium salt via neutralization to the freebase and subsequent complexation with valsartan in iPrOAc/ acetone. Addition of NaOH and crystallization then provided the desired trisodium salt hemihydrate.

Synthesis_1038924-61-6

sacubitril synthesis

72479-05-1
144432-80-4
1038924-61-6
Synthesis of sacubitril from (S)-5-(BROMOMETHYL)-2-PYRROLIDINONE and 4-BIPHENYLBORONIC ACID, PINACOL ESTER

sacubitril Preparation Products And Raw materials

Raw materials

1-Pyrrolidinecarboxylic acid, 2-([1,1'-biphenyl]-4-ylmethyl)-5-oxo-, 1,1-dimethylethyl ester, (2S)- (S)-5-(CHLOROMETHYL)PYRROLIDIN-2-ONE 2-Pyrrolidinone, 5-(iodomethyl)-, (5S)- (S)-5-[(Biphenyl-4-yl)carbonyl]pyrrolidin-2-one (S)-(+)-5-(Hydroxymethyl)-2-pyrrolidinone p-toluenesulfonate
LCZ696 interMediate (S)-5-(BROMOMETHYL)-2-PYRROLIDINONE BOC-D-4,4'-BIPHENYLALANINE 2-BIPHENYLMAGNESIUM BROMIDE 4-BIPHENYLBORONIC ACID, PINACOL ESTER
Magnesium 4-Bromobiphenyl Copper(I) Cyanide

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Preparation Products

sacubitril Suppliers

Global( 49)Suppliers
Supplier Tel Email Country ProdList Advantage
Henan Tianfu Chemical Co.,Ltd. 		+86-0371-55170693 +86-19937530512 info@tianfuchem.com China 21691 55
career henan chemical co 		+86-0371-86658258 sales@coreychem.com China 29914 58
Biochempartner 		0086-13720134139 candy@biochempartner.com CHINA 967 58
Chongqing Chemdad Co., Ltd 		+86-023-61398051 +8613650506873 sales@chemdad.com China 39916 58
Shanghai Rochi Pharmaceutical Co.,Ltd. 		21-38751876 +8615000076078 info@rochipharma.com China 431 58
ANHUI WITOP BIOTECH CO., LTD 		+8615255079626 eric@witopchemical.com China 23556 58
Dideu Industries Group Limited 		+86-29-89586680 +86-15129568250 1026@dideu.com China 29220 58
Dayang Chem (Hangzhou) Co.,Ltd. 		571-88938639 +8617705817739 info@dycnchem.com CHINA 52867 58
changzhou huayang technology co., ltd 		+8615250961469 2571773637@qq.com China 9821 58
sgtlifesciences pvt ltd 		+8617013299288 dj@sgtlifesciences.com China 12382 58
Supplier Advantage
Henan Tianfu Chemical Co.,Ltd. 		55
career henan chemical co 		58
Biochempartner 		58
Chongqing Chemdad Co., Ltd 		58
Shanghai Rochi Pharmaceutical Co.,Ltd. 		58
ANHUI WITOP BIOTECH CO., LTD 		58
Dideu Industries Group Limited 		58
Dayang Chem (Hangzhou) Co.,Ltd. 		58
changzhou huayang technology co., ltd 		58
sgtlifesciences pvt ltd 		58

View Lastest Price from sacubitril manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
sacubitril pictures 2021-10-28 sacubitril
1038924-61-6
 US $1.10 / g 1g 99.00% 100 Tons Min Dideu Industries Group Limited
sacubitril pictures 2019-07-06 sacubitril
1038924-61-6
 US $1.00 / KG 1KG 99% 100kg Career Henan Chemical Co
  • sacubitril pictures
  • sacubitril
    1038924-61-6
  • US $1.10 / g
  • 99.00%
  • Dideu Industries Group Limited
  • sacubitril pictures
  • sacubitril
    1038924-61-6
  • US $1.00 / KG
  • 99%
  • Career Henan Chemical Co

1038924-61-6(sacubitril)Related Search:

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((R)-2-biphenyl-4-yl-1-forMylethyl)carbaMic acid t-butyl ester (2R,4S)-ethyl 5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpentanoate (2R,4S)-4-([1,1'-Biphenyl]-4-ylmethyl)-2-methyl-4-(2,5-dioxopyrrolidin-1-yl)butanoic acid (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-aMino-2-Methylpentanoic acid hydrochloride (R,E)-5-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)aMino)-2-Methylpent-2-enoic acid
(S)-5-[(Biphenyl-4-yl)methyl]-1-(2,2-dimethylpropionyl)pyrrolidin-2-one (2S,4S)-5-(Biphenyl-4-yl)-4-[(tert-butoxycarbonyl)amino]-2-methylpentanoic acid 2-Pyrrolidinone, 5-([1,1'-biphenyl]-4-ylMethyl)-3-Methyl-, (3R,5S)- (2R,4S)-4-([1,1'-Biphenyl]-4-ylmethyl)-4-(4-ethoxy-4-oxobutanamido)-2-methylbutanoic acid Ethyl (2R,4S)-4-([1,1'-biphenyl]-4-ylmethyl)-2-methyl-4-(2,5-dioxopyrrolidin-1-yl)butanoate
LCZ696 LCZ696 InteMediate LCZ Impurity

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sacubitril (S)-5-[(biphenyl-4-yl)Methyl]pyrrolidin-2-one (S)-5-([1,1'-biphenyl]-4-ylMethyl)pyrrolidin-2-one 2-Pyrrolidinone, 5-([1,1'-biphenyl]-4-ylmethyl)-, (5S)- sacubitril ISO 9001：2015 REACH 1038924-61-6