473927-63-8

Basic information

• Product Name: Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate
• Synonyms: Acetic acid, chloro[(4-Methoxyphenyl)hydrazono]-, ethyl ester, (2Z)-;Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate;(2Z)-2-Chloro-2-[2-(4-methoxyphenyl)hydrazinylidene]acetic acid ethyl ester;Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]acetate;Apixaban I;ethyl (2Z)-2-chloro-2-[2-(4-methoxyphenyl)hydrazin-1-ylidene]acetate;Apixaban Impurity O
• CAS NO: 473927-63-8
• Molecular Formula: C₁₁H₁₃ClN₂O₃
• Molecular Weight: 256.68552
• EINECS: -0
• Mol File: 473927-63-8.mol

Chemical Properties

• Boiling Point: 348.955 °C at 760 mmHg
• Flash Point: 164.842 °C
• Appearance: /
• Density: 1.23
• Vapor Pressure: 0.008Pa at 25℃
• PKA: 11.63±0.10(Predicted)
• CAS DataBase Reference: Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate(473927-63-8)
• EPA Substance Registry System: Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate(473927-63-8)

Safety Data

• Hazardous Substances Data: 473927-63-8(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate is used as an organic synthesis intermediate for the preparation of a wide range of organic compounds. Its unique molecular structure allows it to participate in various chemical reactions, making it a valuable building block in the synthesis of complex organic molecules.
Used in Pharmaceutical Industry:
Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate is used as a pharmaceutical intermediate in the development of new drugs and pharmaceutical products. Its ability to be incorporated into the molecular structures of various pharmaceutical compounds makes it an essential component in the drug discovery and development process.
Used in Laboratory Research and Development:
Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate is used in laboratory research and development for the exploration of new chemical reactions and the synthesis of novel compounds. Its unique properties and reactivity make it a valuable tool for researchers working in the fields of organic and pharmaceutical chemistry.
Used in Chemical Production Processes:
Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate is used in chemical production processes to manufacture a variety of chemical products. Its versatility as an intermediate allows it to be incorporated into the production of various chemicals, contributing to the efficiency and effectiveness of these processes.

Synthesis

Preparation of ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate To p-anisidine (16 g, 0.129 mol) in conc. HCL (40 mL), 100 mL) H2O, cooled to -5° C. and sodium nitrite (9.4 g, 0.136 mol) in H2O (60 mL) was added. The reaction mixture was stirred at -5° C. for 20 min and a mixture of ethylchloroacetoacetate (22 g, 0.133 mol), ethanol (100 mL), sodiumacetate (32 g, 0.389 mmol), and H2O (400 mL) was added. The reaction was allowed to warm up to room temperature and stirred for 2h. The product precipitated as a black solid. It was filtered and dried (30 g). 1H-NMR (CDCl3) δ 8.28 (s, 1H), 7.18 (d, 2H), 6.90 (d, 2H), 4.41 (q, 2H), 3.80 (s, 3H), 1.42 (t, 3H) ppm.

Upstream product

• 104-94-9 4-methoxy-aniline 
• 105-39-5 chloroacetic acid ethyl ester 
• 127-09-3 sodium acetate 
• 609-15-4 ethyl 2-chloro-3-oxo-butyrate 

Downstream Products

• 536759-91-8 4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-6-(4-nitrophenyl)-7-oxo- 1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester 
• 473927-64-9 1-(4-methoxy-phenyl)-6-(4-iodo-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester 
• 1423803-24-0 6-(4-aminophenyl)-1-(4-methoxyphenyl)-(4-methoxyphenyl)-7-carbonyl-1H-pyrazolo[3,4-c]-4,5,6,7-tetrahydropyridine-3-amide 
• 1449510-64-8 6-(4-(5-chloropentanamido)phenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide 
• 503614-56-0 1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3, 4-c]pyridine-3-carboxylic acid ethyl ester 
• 503614-91-3 1-(4-methoxy-phenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester 
• 764659-60-1 1-(4-methoxyphenyl)-6-(4-cyanophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester 

Relevant articles and documents

Preparation method of (Z)-[(4-methoxyphenyl)hydrazono]ethyl chloroacetate

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

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

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

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

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

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

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

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

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

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.