365998-36-3

Basic information

• Product Name: (5H-Pyrrolo[3,4-d]thiazole-5-carboxylic acid,2-[[[(1R,2S,5S)-2-[[(5-chloro-1H-indol-2-yl)carbonyl]aMino]-5-[(diMethylaMino)carbonyl]cyclohexyl]aMino]carbonyl]-4,6-dihydro-,1,1-diMethylethyl ester
• Synonyms: (5H-Pyrrolo[3,4-d]thiazole-5-carboxylic acid,2-[[[(1R,2S,5S)-2-[[(5-chloro-1H-indol-2-yl)carbonyl]aMino]-5-[(diMethylaMino)carbonyl]cyclohexyl]aMino]carbonyl]-4,6-dihydro-,1,1-diMethylethyl ester;Edoxaban INTERMEDIATES Ⅰ;Edoxaban INTERMEDIATES Ⅱ;Edoxaban INTERMEDIATES Ⅲ;EthanediaMide iMpurity A;CarbaMic acid, N-[(1R,2S,5S)-2-aMino-5-[(diMethylaMino)carbonyl]cyclohexyl]-, 1,1-diMethylethyl ester;InterMediate of Edoxaban;tert-Butyl [(1R,2S,5S)-2-amino-5-[(dimethylamino)carbonyl]cyclohexyl]carbamate
• CAS NO: 365998-36-3
• Molecular Formula: C₁₄H₂₇N₃O₃
• Molecular Weight: 285.38248
• EINECS: 1592732-453-0
• Mol File: 365998-36-3.mol

Chemical Properties

• Boiling Point: 434.4±45.0 °C(Predicted)
• Appearance: /
• Density: 1.09±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C(protect from light)
• PKA: 11.90±0.60(Predicted)
• CAS DataBase Reference: (5H-Pyrrolo[3,4-d]thiazole-5-carboxylic acid,2-[[[(1R,2S,5S)-2-[[(5-chloro-1H-indol-2-yl)carbonyl]aMino]-5-[(diMethylaMino)carbonyl]cyclohexyl]aMino]carbonyl]-4,6-dihydro-,1,1-diMethylethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (5H-Pyrrolo[3,4-d]thiazole-5-carboxylic acid,2-[[[(1R,2S,5S)-2-[[(5-chloro-1H-indol-2-yl)carbonyl]aMino]-5-[(diMethylaMino)carbonyl]cyclohexyl]aMino]carbonyl]-4,6-dihydro-,1,1-diMethylethyl ester(365998-36-3)
• EPA Substance Registry System: (5H-Pyrrolo[3,4-d]thiazole-5-carboxylic acid,2-[[[(1R,2S,5S)-2-[[(5-chloro-1H-indol-2-yl)carbonyl]aMino]-5-[(diMethylaMino)carbonyl]cyclohexyl]aMino]carbonyl]-4,6-dihydro-,1,1-diMethylethyl ester(365998-36-3)

Safety Data

• Hazardous Substances Data: 365998-36-3(Hazardous Substances Data)

Usage

Uses

tert-Butyl [(1R,2S,5S)-2-Amino-5-[(dimethylamino)carbonyl]cyclohexyl]carbamate is a reagent used in the synthesis of cis-1,2-diaminocyclohexane derivative, which are factor Xa (fXa) inhibitors.

Upstream product

• 480450-69-9 tert-butyl N-[(1R,2S,5S)-2-azido-5-[(dimethylamino)carbonyl]cyclohexyl]carbamate 
• 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 
• 139893-81-5 (1S,4S,5S)-4-bromo-6-oxabicyclo<3.2.1>octan-7-one 
• 67976-82-3 (1S)-3-cyclohexene-1-carboxylic acid (R)-(+)-α-methylbenzylamine salt 
• 5708-19-0 (1S)-3-cyclohexenecarboxylic acid 
• 4771-80-6 1,2,5,6-tetrahydrobenzoic acid 
• 19914-91-1 (1RS,4RS,5RS)-4-bromo-6-oxabicyclo<3.2.1>octan-7-one 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 480452-40-2 tert-Butyl (1R,2S,5S)-5-[(dimethylamino)carbonyl]-2-{[2-(4-fluoroanilino)-2-oxoethanethioyl]amino}cyclohexyl-carbamate 
• 480449-95-4 (1S,2R,4S)-N₂-(tert-Butoxycarbonyl)-N₁-[(6-chloro-quinolin-2-yl)carbonyl]-4-(N,N-dimethylcarbamoyl)-1,2-cyclohexanediamine 
• 480451-79-4 tert-Butyl (1R,2S,5S)-2-{[2-(4-chloroanilino)-2-(hydroxyimino)acetyl]amino}-5-[(dimethylamino)carbonyl]-cyclohexylcarbamate 
• 500571-54-0 Methyl 2-[((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)amino]-2-(methoxyimino)-acetate 
• 480450-94-0 t-butyl {(1R,2S,5S)-2-{[(5-chloro-3-fluoroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}carbamate 
• 1227058-05-0 tert-butyl (1R,2S,5S)-2-{[(7-chloroimidazo[1,2-a]pyridin-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexylcarbamate 
• 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 
• 480449-70-5 edoxaban 
• 480449-71-6 [14C]-Edoxaban tosylate 
• 1353893-22-7 tert-butyl {(1R,2S,5S)-2-amino-5-[(dimethylamino)carbonyl]cyclohexyl}carbamate monooxalate monohydrate 

Relevant articles and documents

Method for preparing eteaban chiral amine intermediate (by machine translation)

The invention provides a safe and convenient method for preparing N - [(1R, 2S, 5S) -2 - amino -5 - [(dimethylamino) carbonyl] cyclohexyl] carbamic acid tert-butyl formate. The compound N - [(1R, 2R, 5S) -5 - [(dimethylamino) carbonyl] -2 - hydroxycyclohexyl] carbamic acid tert-butyl carbamate and the DBU azidate are then reacted to obtain N - [(1R, 2R, 5S) -5 - [(dimethylamino) carbonyl] cyclohexyl] carbamic acid tert-butyl formate in the presence of DBU to obtain the corresponding amino. N - [(1R, 2S, 5S) -2 - amino -2 -5 - [(dimethylamino) carbonyl] cyclohexyl] carbamic acid tert-butyl formate in the presence of a DBU to obtain the corresponding amino compound. N - 2S [(dimethylamino) carbonyl] cyclohexyl] carbamic acid tert-butyl formate 1R 5S -2 -5 . (by machine translation)

Preparation method of edoxaban intermediate

The invention relates to the technical field of medicines, and particularly discloses a preparation method of an edoxaban intermediate. The preparation method comprises the following steps: carrying out diene synthesis on a thiophene derivative of a compound II and acrylic acid, and carrying out chiral resolution to obtain a compound IV; carrying out amidation reaction with dimethylamine hydrochloride to obtain a compound V; reacting with di-tert-butyl dicarbonate in a hydrogen atmosphere to obtain a compound VI and a compound VI'; and carrying out amino deprotection and chiral resolution to obtain a compound I, namely the edoxaban intermediate. The preparation method provided by the invention has the advantages of concise operation steps, high diastereomer selectivity, facilitation of improvement of the product yield and reduction of the production cost, no use of a dangerous reagent sodium azide, no involvement of a low-temperature reaction, reduction of the production risk, and guarantee of the safety and the operability of the reaction.

Development of an Efficient Manufacturing Process for a Key Intermediate in the Synthesis of Edoxaban

We report the development of a novel synthetic method to access a key intermediate in the synthesis of edoxaban. The main features of the new synthetic method are an improvement in the approach for the synthesis of a key chiral bromolactone, application of an interesting cyclization reaction utilizing neighboring group participation to construct a differentially protected 1,2-cis-diamine, and implementation of plug-flow reactor technology to enable the reaction of an unstable intermediate on multihundred kilogram scale. The overall yield for the preparation of edoxaban was significantly increased by implementing these changes and led to a more efficient and environmentally friendly manufacturing process.

Preparation method and intermediate of chiral diamine compound

The present invention relates to a preparation method and an intermediate of a chiral diamine compound, wherein the chiral diamine compound is used for preparing the key intermediate of a small molecule oral anticoagulant edoxaban. According to the present invention, the steps of the preparation method of the chiral diamine compound 2 and the key intermediate 2B are defined in the specification, wherein the group R is preferably selected from methoxy, ethoxy and dimethylamino.

Imide intermediate compound as well as preparation method and application thereof

The invention discloses an imide intermediate compound adopting a structure shown as a formula (II) and a preparation method of the imide intermediate compound. The imide intermediate compound can beused as an intermediate for preparing a precursor compound of an anticoagulant edoxaban. The preparation method comprises the following steps: adding a compound adopting a structure shown as a formula(I) into a reaction solvent, introducing a compound containing a nucleophilic amino group into a compound adopting the structure shown as the formula (I) under the action of an azo reagent and ternary substituted phosphorus, converting a hydroxyl group at 1st position into an amino group, and reversing the configuration to obtain the intermediate adopting the structure shown as the formula (II);adding the imide intermediate in alkali, and removing a protecting group to obtain the precursor compound, adopting the structure shown as a formula (III), of the edoxaban. Use of explosive or highlytoxic compounds in the preparation process and a subsequent high-pressure hydrogenation reaction are avoided, not only the chiral purity of a product is greatly improved, but also the production costcan be reduced, safety hazards in the production process are solved, the production cycle is greatly shortened, and the production efficiency is significantly improved.

METHOD FOR PRODUCING (1S,4S,5S)-4-BROMO-6-OXABICYCLO[3.2.1]OCTAN-7-ONE

It is an object of the present invention to provide a method for efficiently producing (1S,4S,5S)-4-bromo-6-oxabicyclo[3.2.1]octan-7-one (1), which is important as an intermediate compound for the production of an FXa-inhibiting compound. A method for producing (1S,4S,5S)-4-bromo-6-oxabicyclo[3.2.1]octan-7-one (1), which comprises treating an (R)-α-phenylethylamine salt of (S)-3-cyclohexene-1-carboxylic acid with 1,3-dibromo-5,5-dimethylhydantoin or N-bromosuccinimide in a solvent.

A method for producing an optically active Dimamine deriv.

The problem to be solved is to provide a method for efficiently producing compounds (1) and (1a) that are important intermediate compounds in the production of FXa inhibitors (X) and (X-a). The solutions thereto are a method for producing a compound represented by the formula (8d) using a stereoselective intramolecular cyclization reaction, and a method for producing a compound (If) or a salt thereof, or a hydrate thereof, which is characterized by desulfonylation of the compound (8d). In each formula, R 4a represents a C1-C6 alkyl group, a benzyl group, etc.

PROCESS FOR PRODUCING DIAMINE DERIVATIVE

The problem to be solved is to provide an important intermediate for production of an FXa inhibitor. The solution thereto is a process for industrially producing a compound (1) represented by the following formula (1): wherein Boc represents a tert-butoxycarbonyl group.

Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part I: Exploration of 5-6 fused rings as alternative S1 moieties

A series of cis-1,2-diaminocyclohexane derivatives were synthesized with the aim of optimizing previously disclosed factor Xa (fXa) inhibitors. The exploration of 5-6 fused rings as alternative S1 moieties resulted in two compounds which demonstrated improved solubility and reduced food effect compared to the clinical candidate, compound A. Herein, we describe the synthesis and structure-activity relationship (SAR), together with the physicochemical properties and pharmacokinetic (PK) profiles of some prospective compounds.

DIAMINE DERIVATIVES

A compound represented by formula (1):Q1-Q2-To-N(R1) -Q3-N(R2)-T1-Q4 [wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 represents the following group: (wherein Q5 is an alkylene group having 1 to 8 carbon atoms, or the like); and T0 and T1 are carbonyl groups or the like], a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.