480452-36-6

Basic information

• Product Name: EthanediaMide iMpurity D
• Synonyms: EthanediaMide iMpurity D;tert-Butyl(1R,2S,5S)-2-({2-[(5-chloropyridin-2-yl)aMino]-2-oxoacetyl}aMino)-5-[(diMethylaMino)carbonyl]cyclohexyl-carbaMate;N1-(5-chloropyridin-2-yl)-N2-((1S,2R,4S)-2-[(tert-Butoxycarbonyl)Amino ]-4-[(dimethylamino)carbonyl]-cyclohexyl) oxalamide;Edoxaban Impurity 6;Edoxaban impurity D
• CAS NO: 480452-36-6
• Molecular Formula: C₂₁H₃₀ClN₅O₅
• Molecular Weight: 88.06536
• Mol File: 480452-36-6.mol

Chemical Properties

• Appearance: /
• Density: 1.29±0.1 g/cm3(Predicted)
• PKA: 9.46±0.70(Predicted)
• CAS DataBase Reference: EthanediaMide iMpurity D(CAS DataBase Reference)
• NIST Chemistry Reference: EthanediaMide iMpurity D(480452-36-6)
• EPA Substance Registry System: EthanediaMide iMpurity D(480452-36-6)

Safety Data

• Hazardous Substances Data: 480452-36-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
EthanediaMide iMpurity D is used as an impurity in the development and manufacturing process of Edoxaban for its role in blood clot prevention and treatment. The presence of this impurity is essential for the proper functioning and effectiveness of the drug, as it contributes to the overall anticoagulant properties of Edoxaban.
As an anticoagulant agent, Edoxaban is used for the prevention and treatment of various blood clot-related conditions, such as deep vein thrombosis, pulmonary embolism, and stroke. The presence of EthanediaMide iMpurity D in Edoxaban enhances its ability to inhibit factor Xa, a key enzyme in the coagulation cascade, thus reducing the risk of blood clot formation and associated complications.

Upstream product

• 480450-69-9 tert-butyl N-[(1R,2S,5S)-2-azido-5-[(dimethylamino)carbonyl]cyclohexyl]carbamate 
• 1072-98-6 5-chloro-2-pyridylamine 
• 929693-35-6 (1S,3S,6R)-N,N-dimethyl-7-oxabicyclo[4.1.0]heptane-3-carboxamide 
• 929693-36-7 (1S,3R,4R)-3-amino-4-hydroxy-N,N-dimethyl cyclohexanecarboxamide 
• 929693-30-1 (1S,3R,4R)-3-[(tert-butoxycarbonyl)amino]-4-hydroxy-N,N-dimethylcyclohexanecarboxamide 
• 929693-31-2 {(1R,2R,4S)-2-[(tert-butoxycarbonyl)amino]-4-[(dimethylamino)carbonyl]cyclohexyl}methanesulfonate 
• 365998-36-3 (1S,2R,4S)-N₂-(tert-butoxycarbonyl)-4-(N,N-dimethylcarbamoyl)-1,2-cyclohexanediamine 
• 139893-81-5 (1S,4S,5S)-4-bromo-6-oxabicyclo<3.2.1>octan-7-one 
• 5708-19-0 (1S)-3-cyclohexenecarboxylic acid 
• 67976-82-3 (1S)-3-cyclohexene-1-carboxylic acid (R)-(+)-α-methylbenzylamine salt 
• 552850-73-4 2-((5-chloropyridin-2-yl)amino)-2-oxoacetic acid 
• 365997-36-0 (1S,3R,4R)-3-[(tert-butoxycarbonyl)amino]-4-[(methylsulfonyl)oxy]cyclohexanecarboxylic acid ethyl ester 
• 365997-34-8 ethyl (1S,3R,4S)-4-azido-3-(tert-butoxycarbonylamino)-cyclohexane-1-carboxylate 

Downstream Products

• 480449-70-5 edoxaban 
• 480449-71-6 [14C]-Edoxaban tosylate 
• 480452-37-7 N¹-[(1S,2R,4S)-2-amino-4-[(dimethylamino)carbonyl]cyclohexyl]-N²-(5-chloro-2-pyridyl)ethanediamide 

Relevant articles and documents

Preparation method of edoxaban and intermediate thereof

The invention relates to a preparation method of edoxaban and an intermediate thereof. A compound 1, a compound 2 and a compound 5 which are taken as initial raw materials are subjected to an ammonolysis reaction, a deprotection reaction, a carboxylation reaction and a condensation reaction to generate edoxaban. Compared with the prior art, the preparation method is higher in operability and safety during amplified production, and the obtained product is high in yield and purity.

PROCESS FOR PREPARATION OF EDOXABAN

The present invention relates to process for preparation N1-(5-Chloropyridin-2-yl)-N2-[(1S,2R,4S)-4-(N,N-dimethylcarbamoyl)-2-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-ylcarboxamido)cyclohexyl]oxamide p-toluene sulfonate monohydrate [edoxaban tosylate monohydrate], the compound of formula (I), comprising reacting compound of formula (VI) with compound of formula (V) to obtain the compound of formula (IV) and further converting it to edoxaban tosylate monohydrate in an industrially feasible process.

Preparation method of edoxaban tosylate and isomers thereof

The invention discloses a preparation method of edoxaban tosylate and isomers thereof. By taking a compound (I) and a compound (II) as starting materials, the method can be used to prepare any one ofhigh-purity edoxaban tosylate (1S, 2R, 4S), edoxaban tosylate enantiomers (1R, 2S, 4R), edoxaban tosylate epimers (1R, 2R, 4S) and edoxaban tosylate epimers (1S, 2S, 4R). Effective guarantee is provided for process research and quality control of the edoxaban tosylate bulk drug and related preparations, the preparation method is suitable for commercialization, the produced edoxaban tosylate bulk drug is high in purity and has great significance and practical value, and the production of the edoxaban tosylate bulk drug and the control of drug quality are facilitated.

Improved preparation method of edoxaban intermediate

The invention belongs to the field of organic synthesis, and particularly relates to an improved preparation method of an edoxaban intermediate. In most preparation methods for preparing the compound(1), a system is extremely easy to be in a cured state in the reaction process, the system is difficult to stir, and finally, the problems of product yield reduction, quality deterioration and the like are caused. In order to solve the problem of curing in the system, the improved preparation method of an edoxaban intermediate is expected to be provided. In the process of synthesizing the compound(1), alcohol or a mixture of alcohol and acetonitrile is used as a reaction solvent, so that the reaction system is in a clear state at the beginning, the product is gradually separated out along with the reaction, the product is uniformly dispersed in the solvent in the whole process from the beginning to the end of the reaction and is easy to stir, and the curing problem in the reaction processis effectively solved.

Method for preparing edoxaban from trichloroacetophenone onium salt derivatives

The invention provides a method for preparing edoxaban by using 2, 2, 2-trichloro-1-(4, 5, 6, 7-tetrahydro-5-methylthiazolo[5, 4-c]pyridinium-1-yl) ethanone chloride. The preparation method comprisesthe following steps: preparing 2, 2, 2-trichloro-1-(4, 5, 6, 7-tetrahydro-5-methylthiazolo[5, 4-c]pyridinium-1-yl) ethanone chloride, namely 109C5-11; the invention discloses a preparation method of N1[(1S, 2R, 4S)-2-amino-4-[(dimethylamino) carbonyl]cyclohexyl]-N2(5-chloro-2-pyridyl) oxalamide dimesylate, namely 109T2-31. The 109C5-11 is used as an acylation reagent to prepare the edoxaban with 109T2-31. The preparation method comprises the following steps: preparing the edoxaban by using the 109C5-11 as the acylation reagent; the novel method overcomes the defect that expensive condensing agents EDCI.HCl and activating agents HOBt need to be used in the prior art. The new method provided by the invention is beneficial to more economically and more efficiently realizing industrial scale production of the Edoxaban p-toluenesulfonate hydrate.

METHOD FOR PREPARING TERT-BUTYL N-((1R,2S,5S)-2-((2-((5-CHLOROPYRIDIN-2-YL)AMINO)-2-OXOACETYL)AMINO)-5-(DIMETHYLCARBAMOYL)CYCLOHEXYL)CARBAMATE

The present invention relates to a method for preparing tert-butyl N- ((1R,2S,5S)-2-((2-((5-chloropyridin-2-yl)amino)-2-oxoacetyl)amino) -5-(dimethylcarbamoyl)cyclohexyl)carbamate of formula (I), or a salt or solvate thereof,characterized in that it comprises the steps of a) mixing tert-butyl N-((1R,2S,5S)-2-amino-5-(dimethylcarbamoyl) cyclohexyl)carbamate of formula (A) with ethyl 2-((5-chloropyridin-2- yl)amino)-2-oxoacetate of formula (B) in an organic solvent; b) mixing a base with the resulting mixture of step (a); and c) stirring the mixture obtained in step (b). The method substantially facilitates the obtention of the compound of formula (I), leading to a reduction in the viscosity of the reaction medium and improving product yield and/or product purity. Formulae (I), (B), (A).

METHOD OF PRODUCING EDOXABAN

PROBLEM TO BE SOLVED: To provide a method of producing edoxaban, which exhibits FXa inhibitory effect and is useful as an agent for preventing and/or treating a thrombotic and/or embolic disease, where the method realizes low cost, high reaction efficiency, reduced time consumption, and high product purity and is suitable for large-scale industrial production. SOLUTION: A method of producing edoxaban (formula 1) includes a method illustrated by the reaction formula in the figure. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT

Preparation method of edoxaban p-toluenesulfonate monohydrate

The invention provides a preparation method of edoxaban p-toluenesulfonate monohydrate. According to the preparation method, an appropriate amount of a specific ionic liquid is added, a specific ratioof a combination of triethylamine and pyridine is selected as a base, the rapid progress of a reaction is facilitated, and improvements on the production rate and the product purity are facilitated.

Preparation method of antithrombotic drug

The invention relates to a preparation method of an antithrombotic drug, belongs to the technical field of medicinal chemistry and in particular relates to a preparation method of a direct coagulationfactor Xa inhibitor, which is shown as the following reaction. Compared with the existing process, the preparation method has the advantages of mild reaction condition in each step, high yield, simplicity and convenience operation, stable process and suitability for large-scale industrial production.

SALT OF AMINE-PROTECTED (1S,2R,4S)-1,2-AMINO-N,N-DIMETHYLCYCLOHEXANE-4-CARBOXAMIDE

Disclosed are compounds and methods for the preparation of Edoxaban. In particular, a camphor sulfonate salt of an amine-protected [(1R,2S,5S)-1,2-amino-5-[(dimethylamino)carbonyl] cyclohexane, an intermediate that may be formed in the synthesis of Edoxaban, is disclosed as well as methods of its preparation.