- Preparation method of edoxaban chiral azide intermediate compound
-
The invention provides a preparation method of an edoxaban chiral azide intermediate compound, which comprises the following steps of: performing substitution reaction on a hydroxyl compound as shown in a formula (II) serving as a substrate and an organic azide compound in an organic solvent in the presence of an amidine structure compound to obtain a chiral azide intermediate compound as shown in a formula (I). A two-step synthesis reaction is directly optimized into one-step reaction synthesis, organic azide compounds such as diphenyl azide phosphate, p-toluenesulfonyl azide and azido trimethylsilane are adopted as sources of azide groups, and a substitution reaction is carried out in a proper solvent under the assistance of amidine structure compounds such as methylimidine, DBN, DBU and trinitrogen amidine to obtain a target compound, namely, a chiral azide intermediate. Not only is the use of highly toxic methylsulfonyl chloride and explosive sodium azide successfully avoided, but also the process difficulty and the production cost are reduced.
- -
-
Paragraph 0009; 0024-0026; 0029-0038
(2021/10/27)
-
- 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.
- -
-
-
- 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)
- -
-
Paragraph 0055-0058
(2020/09/12)
-
- 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.
- -
-
-
- 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.
- -
-
Paragraph 0199-0201
(2016/10/09)
-
- PROCESS FOR PREPARATION OF OPTICALLY ACTIVE DIAMINE DERIVATIVE SALT
-
The problem to be solved is to produce, at high yields with high purity, anhydrous crystals of a compound represented by formula (1) that is an important intermediate for preparation of FXa inhibitor compound (X) or a pharmacologically acceptable salt thereof, or a hydrate thereof. The solution thereto is an industrial preparation process that provides, with high purity, anhydrous crystals of a compound represented by the following formula (1), which is an intermediate for the production of FXa inhibitor compound (X) or a pharmacologically acceptable salt thereof, or a hydrate thereof, wherein Boc represents a tert-butoxycarbonyl group.
- -
-
-
- METHOD FOR PRODUCING OPTICALLY ACTIVE DIAMINE DERIVATIVE
-
The problem to be solved is to provide an important intermediate for production of an FXa inhibitor. The solution thereto is a method for industrially producing a compound (1) or a compound (4), comprising: [Step 1]: adding a quaternary ammonium salt and a metal azide salt to water to prepare an aqueous solution of an azidification reagent complex comprising quaternary ammonium salt-metal azide salt, and subsequently dehydrating the aqueous solution using an aromatic hydrocarbon solvent to form a mixed solution of the azidification reagent complex comprising quaternary ammonium salt-metal azide salt and the aromatic hydrocarbon solvent with a water content of 0.2% or less; and [Step 2]: adding, to the mixed solution prepared in [Step 1], a compound (2) wherein L represents a leaving group.
- -
-
Page/Page column 23-24
(2012/02/04)
-
- 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.
- -
-
Page/Page column 14
(2012/02/04)
-
- 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.
- Yoshikawa, Kenji,Yokomizo, Aki,Naito, Hiroyuki,Haginoya, Noriyasu,Kobayashi, Shozo,Yoshino, Toshiharu,Nagata, Tsutomu,Mochizuki, Akiyoshi,Osanai, Ken,Watanabe, Kengo,Kanno, Hideyuki,Ohta, Toshiharu
-
experimental part
p. 8206 - 8220
(2010/04/06)
-
- DIAMINE DERIVATIVES
-
A compound represented by the general formula (1):Q1-Q2-T0-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 is a group in which 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 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.
- -
-
-