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
• Article Data: 13

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

Ethyl (2Z)-chloro[(4-methoxyphenyl)hydrazono]ethanoate can be used as organic synthesis intermediates and pharmaceutical intermediates, mainly used in laboratory research and development and chemical and pharmaceutical production 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 
• 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 
• 503614-56-0 1-(4-methoxyphenyl)-7-oxo-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

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.

PROCESS FOR THE PREPARATION OF APIXABAN

The present disclosure provides processes and intermediates for the preparation of apixaban.