480452-37-7

Basic information

• Product Name: EthanediaMide iMpurity F
• Synonyms: EthanediaMide iMpurity F;N1-(5-chloropyridin-2-yl)-N2-((1S,2R,4S)-2-[(tert-Butoxycarbonyl)Amino ]-4-[(dimethylamino)carbonyl]-cyclohexyl) oxalamide dimethanesulfonate;Edoxaban Impurity 5
• CAS NO: 480452-37-7
• Molecular Formula: C₁₆H₂₂ClN₅O₃
• Molecular Weight: 88.06536
• Mol File: 480452-37-7.mol

Chemical Properties

• Appearance: /
• Density: 1.34±0.1 g/cm3(Predicted)
• PKA: 9.46±0.70(Predicted)
• CAS DataBase Reference: EthanediaMide iMpurity F(CAS DataBase Reference)
• NIST Chemistry Reference: EthanediaMide iMpurity F(480452-37-7)
• EPA Substance Registry System: EthanediaMide iMpurity F(480452-37-7)

Safety Data

• Hazardous Substances Data: 480452-37-7(Hazardous Substances Data)

Upstream product

• 349125-08-2 ethyl 2-((5-chloropyridin -2-yl)amino)-2-oxoacetate 
• 365998-36-3 (1S,2R,4S)-N₂-(tert-butoxycarbonyl)-4-(N,N-dimethylcarbamoyl)-1,2-cyclohexanediamine 
• 1072-98-6 5-chloro-2-pyridylamine 
• 480452-36-6 carbamic acid, N-[(1R,2S,5S)-2-[[2-[(5-chloro-2-pyridinyl)amino]-2-oxoacetyl]amino]-5-[(dimethylamino)carbonyl]cyclohexyl]-1,1-dimethylethyl ester 

Downstream Products

• 480449-70-5 edoxaban 
• 480449-71-6 [14C]-Edoxaban tosylate 

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.

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 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

The invention relates to a new preparation route and a new method for a p-toluenesulfonic acid edoxaban hydrate and intermediates thereof. The new method comprises the steps that a high-reactivity compound 109A4x is prepared; a compound 109C6x is prepared by using a new synthesizing method; new compounds 109E8-01, 109E9x and 109T7-01 are prepared; the p-toluenesulfonic acid edoxaban hydrate is prepared by using the intermediates. By using the new method and the new route, the reaction step of copious cooling is omitted, and dangerous elemental sulfur, high-risk n-butyllithium and high-risk azides are prevented from being used. In a word, by means of the method, the p-toluenesulfonic acid edoxaban hydrate and the key intermediates thereof are more easily and safely prepared at a lower coston an industrialization scale.

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.

PROCESS FOR PRODUCING DIAMINE DERIVATIVE

The present invention provides a low-toxic and high-recovery industrial process for synthesizing an optically active diamine derivative represented by formula (D), the process comprising the steps of: (a) mixing a compound represented by formula (A) and a compound represented by formula (C) in organic solvents and secondary amine; (b) reaction under heating; (c) cooling and adding water to the mixed solution, allowing it to crystallize to obtain the compound represented by formula (D).

Preparation method for free-state edoxaban

The invention discloses a preparation method for free-state edoxaban.The synthetic route is shown in the description.According to the preparation method, the charging sequence is changed, and a curing problem caused by a traditional method is reduced; according to an existing method, a starting material A and triethylamine are added at first, a starting material B is added, a large amount of solid will appear in the temperature increasing process, and the stirring uniformity is greatly affected, so that the yield is greatly lowered, and the method is adopted for greatly solving the problem and improving the yield; when the compound free-state edoxaban is synthetized, a first amount of a saturated sodium bicarbonate water solution is added at first, the phenomenon that a product is rapidly separated out and impurities are included due to the fact that the added saturated sodium bicarbonate water solution is excessive is avoided, and meanwhile introduction of genotoxicity impurity methanesulfonate is effectively avoided; after the impurities are completely hydrolyzed, a second amount of the saturated sodium bicarbonate water solution is added so that the product can be separated out thoroughly; the method improves the crystallization way, the yield is improved, and generation of impurities is reduced.