149709-63-7

Basic information

• Product Name: LCZ 696 Impurity C
• Synonyms: LCZ 696 Impurity C;(2S,4S)-Sacubitril;4-(((2S,4S)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoic acid;[1,1'-Biphenyl]-4-pentanoic acid, γ-[(3-carboxy-1-oxopropyl)amino]-α-methyl-, ethyl ester, [S-(R*,R*)]- (9CI);Sacubitril Impurity C
• CAS NO: 149709-63-7
• Molecular Formula: C24H29NO5
• Molecular Weight: 411.49076
• Mol File: 149709-63-7.mol

Chemical Properties

• Boiling Point: 656.9±55.0 °C(Predicted)
• Appearance: /
• Density: 1.151±0.06 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 4.72±0.10(Predicted)
• Stability: Moisture Sensitive
• CAS DataBase Reference: LCZ 696 Impurity C(CAS DataBase Reference)
• NIST Chemistry Reference: LCZ 696 Impurity C(149709-63-7)
• EPA Substance Registry System: LCZ 696 Impurity C(149709-63-7)

Safety Data

• Hazardous Substances Data: 149709-63-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
LCZ 696 Impurity C is used as an impurity in the production of Sacubitril (S080895) for its role in the development of antihypertensive drugs. The presence of this impurity may affect the efficacy, safety, and quality of the final drug product, making it essential to monitor and control its levels during the manufacturing process.
Used in Research and Development:
LCZ 696 Impurity C is used as a research compound to study its properties, potential interactions with other substances, and its role in the overall effectiveness of Sacubitril (S080895) as an antihypertensive drug. This research can help in understanding the drug's mechanism of action, optimizing its formulation, and improving its therapeutic potential.
Used in Quality Control and Regulatory Compliance:
LCZ 696 Impurity C is used as a reference material in the quality control and regulatory compliance processes for Sacubitril (S080895). It helps ensure that the drug meets the required standards for purity, potency, and safety, and that the manufacturing process is consistent and reliable.
Used in Drug Safety Assessment:
LCZ 696 Impurity C is used in drug safety assessment to evaluate the potential risks and side effects associated with its presence in the final drug product. This information is crucial for determining the acceptable levels of the impurity in the drug and for setting appropriate safety guidelines for its use in patients.

Upstream product

• 108-30-5 succinic acid anhydride 
• 753421-85-1 ethyl (γS)-γ-amino-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 108-91-8 cyclohexylamine 
• 149709-68-2 (R)-5-(biphenyl-4-yl)-4-tert-butoxycarbonylamino-2-methylpent-2-enoic acid 
• 92-66-0 4-bromo-1,1'-biphenyl 
• 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 

Downstream Products

• 149709-63-7 α-ethyl (αS,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate 
• 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

The preparation method comprises the following steps 1-11: Wherein. ROH (Formula X) is a chiral alcohol and the like, PG is a hydroxy protecting group, a compound of Formula VI and a compound of Formula V are the chiral auxiliary of the present invention. To the invention, the chiral auxiliary base ROH compound and the chiral alcohol X (Formula VI) are used for preparing the chiral auxiliary base-type compound of formula V IV and the compound of Formula XI, and the compound of formula IV can be prepared through three-step simple operation steps of chiral auxiliary base. Be applicable to industrial production.

Preparation method of sacubitril valsartan sodium

The invention provides a preparation method of sacubitril valsartan sodium, and belongs to the field of medical chemistry. The preparation method comprises the following steps: by using a compound S309A03 as a raw material, carrying out hydrogenation reaction to generate a compound BPA08, reacting the compound BPA08 in ethanol to generate a compound SAC01, reacting the compound SAC01 with succinicanhydride to generate a compound SAC02, optionally reacting the compound SAC02 with sodium hydroxide, and reacting the compound SAC03 with calcium chloride to generate a compound SAC04; and subjecting the compound SAC04 to acid treatment to obtain a compound YJX01, and enabling the compound YJX01 to react with VST in a single solvent in the presence of sodium hydroxide to prepare the compound YJX02. The preparation method disclosed by the invention is simple to operate, the time required by the process is reduced, the total yield of the process route is greatly improved, an unexpected technical effect is obtained, impurities in the process are removed, and a product with higher purity is obtained. The method has mild process conditions and easily available raw materials, and is suitable for industrial amplification.

Preparation method of key component sacubitril of novel anti-heart-failure drug Entresto

The invention relates to a preparation method of a key component sacubitril of a novel anti-heart-failure drug Entresto. The chemical name of sacubitril is 4-(((2S,4R)-1-(1,1'-biphen-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl) amino)-4-oxobutyric acid. According to the method, 4-bromobiphenyl is used as an initial raw material, and the method is simple in process route, low in cost and suitable forindustrial production.

Preparation method of neprilysin inhibitor intermediate

The invention discloses a preparation method for an enkephalinase inhibitor intermediate. According to the preparation method, a target compound with a formula I as described in the specification is prepared by using a compound as shown in a formula IV which is described in the specification as an initial material through a reaction with few steps, wherein the compound with the formula I can be used for preparation of an enkephalinase inhibitor drug namely Sacubtril. In the formula I and the formula IV, R is selected from the group consisting of H, methyl, ethyl or other lower alkyl.

Optimization and process improvement for LCZ696 by employing quality by design (QbD) principles

Efforts toward optimization and improvement for the synthesis of LCZ696 employing design of experiment (DoE) principles are described. By increasing the purity of intermediates and mitigating impurity risk during each step, a telescoped process was developed via removal of isolation of intermediates with the overall yield increased by 28.5% from 45.3% to 73.8%. And the whole production cycle was also shortened from 12 days to 7 days with simplified operations and restored process greenness. Meanwhile, the corresponding impurity profile was thus studied in detail and well documented.

AMMONIUM CARBOXYLATE COMPOUND, CRYSTALLINE FORM, AMORPHOUS FORM AND PREPARATION METHOD THEREOF

The present disclosure belongs to the field of chemical synthesis, and in particular relates to an ammonium carboxylate compound, a crystalline form and an amorphous form, and a preparation method thereof. The present disclosure prepares the compound and the crystalline form I and its single crystal, amorphous form and crystalline form II thereof. The compound, the crystalline forms, the single crystal and the amorphous form can stably exist and exhibit good solid forms, suitable for medicine-making. Furthermore, these products possess high purity and less single impurity. Moreover, the preparation methods of the present disclosure are easy to implement due to the simple processes with mild reaction conditions, and could produce products of high yield and high purity without complex purification steps. Furthermore, the preparation methods may facilitate safety, environmental protection, and industrial production.

SUBSTITUTED BISPHENYL BUTANOIC ESTER DERIVATIVES AS NEP INHIBITORS

The present disclosure provides a compound of Formula (I); or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are defined herein. The disclosure also relates to a method for manufacturing the compounds of the disclosure, and its therapeutic uses. The present disclosure further provides pharmaceutical composition of the compounds of the disclosure and a combination of pharmacologically active agents and a compound of the disclosure.

CRYSTALLINE FORM OF SACUBITRIL, ITS PREPARATION AND USE

The present disclosure relates to a hybrid salt/co-crystal of sacubitril. The present disclosure is also related to processes for the preparation of the hybrid salt/co-crystal of sacubitril. In addition, the present disclosure is related to theuse of the hybrid salt/co- crystal of sacubitril for preparing a pharmaceutical composition.

Method for preparing sacubitril and intermediate thereof

The invention provides a method for preparing sacubitril and an intermediate thereof and belongs to the field of medicine synthesis. The method comprises the following steps: by taking a compound I asa raw material, carrying out an asymmetric reduction reaction under the action of a chiral metallic catalyst so as to obtain an intermediate; finally carrying out a simple synthesis step, thereby obtaining a target product sacubitril. The method is short in synthesis route, easy to implement, high in reaction yield, good in diastereoselectivity, and capable of avoiding relatively tedious aftertreatment steps, and reducing the production cost of the sacubitril while the production efficiency of the sacubitril is improved.

Sacubitril intermediate and preparation method and application thereof

The invention discloses a sacubitril intermediate and a preparation method and application thereof. The sacubitril intermediate has the chemical structure as shown in the formula III and/or formula IV, wherein R is phenyl, benzyl and isopropyl. The application of the intermediate for synthesis of sacubitril has advantages as follows: the preparation process is simple; the reaction condition is mild; and the environment is protected. The invention has great significance and use value for low-cost, large-sale and high-efficiency preparation of high-purity sacubitril.