473927-63-8Relevant articles and documents
Preparation method of (Z)-[(4-methoxyphenyl)hydrazono]ethyl chloroacetate
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Paragraph 0023; 0024; 0025; 0026-0030, (2019/07/16)
The invention discloses a preparation method of intermediate (Z)-[(4-methoxyphenyl)hydrazono]ethyl chloroacetate of apixaban. The method uses p-methoxyaniline and ethyl chloroacetate as starting materials to prepare the product. According to the synthetic method provided by the invention, the product prepared by using the synthetic method has high purity, stable quality, and a high yield; and thesynthetic process is simple, the reaction conditions are mild, the reaction operation is simple and convenient, and the method is green and environmentally friendly and can meet industrialized production requirements of the product.
PROCESS FOR THE PREPARATION OF APIXABAN AND INTERMEDIATES THEREOF
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Paragraph 0146, (2017/06/12)
The present invention refers to novel process for the preparation of Apixaban. Further, the invention also related to a process for the preparation of intermediate of Apixaban from very basic and cheap row material i.e. Aniline which is widely commercially available. The present invention provides process for preparation of Apixaban using a different sequence of synthetic steps and does not involve use of Ullmann reaction.
Process for the preparation of apixaban
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Page/Page column 19, (2017/04/18)
A crystalline Form N-1 of apixaban substantially free from one or more of: 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid; 7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; or methyl 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate, relative to apixaban by area percentage of HPLC and having a mean particle size equal to or greater than 100 μm.
Design, synthesis, and structure–activity relationship of novel and effective apixaban derivatives as FXa inhibitors containing 1,2,4-triazole/pyrrole derivatives as P2 binding element
Wang, Yong,Sun, Xiaoqing,Yang, Di,Guo, Zhuang,Fan, Xuxu,Nie, Minhua,Zhang, Feng,Liu, Yue,Li, Yue,Wang, Yulin,Gong, Ping,Liu, Yajing
, p. 5646 - 5661 (2016/10/24)
Four series of novel and potent FXa inhibitors possessing the 1,2,4-triazole moiety and pyrrole moiety as P2 binding element and dihydroimidazole/tetrahydropyrimidine groups as P4 binding element were designed, synthesized, and evaluated for their anticoagulant activity in human and rabbit plasma in vitro. Most compounds showed moderate to excellent activity. Compounds 14a, 16, 18c, 26c, 35a, and 35b were further examined for their inhibition activity against human FXa in vitro and rat venous thrombosis in vivo. The most promising compound 14a, with an IC50(FXa) value of 0.15?μM and 99% inhibition rate, was identified for further evaluation as an FXa inhibitor.
PROCESS FOR THE PREPARATION OF APIXABAN
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Paragraph 17, (2015/11/10)
The present disclosure provides processes and intermediates for the preparation of apixaban.
Novel intermediate and polymorphs of 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetra hydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide and process thereof
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Paragraph 0132, (2016/01/10)
The present invention provides a novel intermediate as well as novel polymorphs of 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide compound represented by the following structural formula-1 and processes for their preparation.
AN IMPROVED PROCESS FOR THE PREPARATION OF APIXABAN AND INTERMEDIATES THEREOF
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Page/Page column 33, (2015/01/07)
The present invention relates to an improved process for the preparation of apixaban and intermediates thereof. In particular, the invention relates to an improved process for the preparation of an amorphous form of apixaban. The invention also relates to a pharmaceutical composition comprising an amorphous form of apixaban for oral administration as an antithrombotic agent.
Alternate synthesis of apixaban (BMS-562247), an inhibitor of blood coagulation factor Xa
Jiang, Jian'An,Ji, Yafei
, p. 72 - 79 (2012/10/30)
An alternate approach to apixaban was described. The synthesis features a novel and cost-effective synthetic strategy to construct a key N-phenylvalerolactam intermediate 4 from 4-nitroaniline. In addition, the modified synthetic route avoids the use of expensive reagents and significantly improves reaction yields. As demonstrated practically, apixaban was successfully synthesized in overall good yield (35%). Copyright Taylor & Francis Group, LLC.
PYRAZOLE CARBOXAMIDE INHIBITORS OF FACTOR XA
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Page/Page column 30, (2010/04/06)
The present invention relates to new pyrazole carboxamide inhibitors of factor Xa, pharmaceutical compositions thereof, and methods of use thereof.
Molecular design of pyrazolo[3,4-d]pyridazines
Matiichuk,Potopnyk,Obushak
experimental part, p. 1352 - 1361 (2009/09/06)
Reactions of arenediazonium chlorides with ethyl 2-methyl-and 2-chloro-4-oxobutanoates gave, respectively, ethyl 2-(arylhydrazono)propanoates and chloro(arylhydrazono)acetates. Ethyl 2-(arylhydrazono)-propanoates reacted with the Vilsmeier-Haak reagent to give ethyl 1-aryl-4-formyl-1 H-pyrazole-3-carboxylates. Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3- carboxylates were obtained by reaction of chloro(arylhydrazono) acetates with acetylacetone. Reactions of the obtained pyrazole derivatives with hydrazine and methylhydrazine led to the formation of the corresponding 3,4-R 2 1 -6-R2-2-aryl-2,6-dihydro-7H-pyrazolo-[3,4-d]pyridazin-7- ones (R1, R2 = H, Me) which were subjected to alkylation and sulfurization.