3543-74-6

Basic information

• Product Name: 5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester
• Synonyms: Ethyl-4-(5-(bis(2-hydroxyethyl)aMino)-1-Methyl-1H-benzo[d]iMidazol-2-yl)butanoate;5-[Bis(2-hydroxyethyl)aMino]-1-Methyl-2-benziMidazolebutyric Acid Ethyl Ester;4-[5-[Bis(2-hydroxyethyl)aMino]-1-MethylbenziMidazol-2-yl]butanoic acid ethyl ester;ethyl 4-{5-[bis(2-hydroxyethyl)aMino]-1-Methyl-1H-1,3-benzodiazol-2-yl}butanoate;Bendamustine Related Impurity 1;1H-Benzimidazole-2-butanoicacid, 5-[bis(2-hydroxyethyl)amino]-1-methyl-, ethyl ester;5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester;4-{5-[Bis-(2-hydroxy-ethyl)-amino]-1-methyl-1H-benzoimidazol-2-yl}-butyric acidethylester
• CAS NO: 3543-74-6
• Molecular Formula: C18H27N3O4
• Molecular Weight: 349.428
• EINECS: 1308068-626-2
• Product Categories: intermediate;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 3543-74-6.mol
• Article Data: 10

Chemical Properties

• Melting Point: 98-101°C
• Boiling Point: 580.6 °C at 760 mmHg
• Flash Point: 305 °C
• Appearance: /
• Density: 1.21 g/cm³
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 14.26±0.10(Predicted)
• CAS DataBase Reference: 5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester(3543-74-6)
• EPA Substance Registry System: 5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester(3543-74-6)

Safety Data

• Hazardous Substances Data: 3543-74-6(Hazardous Substances Data)

Usage

Description

5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester, also known as Bendamustine Related Impurity 1, is a compound with the CAS number 3543-74-6. It is characterized by its off-white to light tan solid appearance and is primarily used in organic synthesis.

Uses

Used in Pharmaceutical Industry:
5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester is used as an intermediate compound for the synthesis of pharmaceuticals, specifically in the production of bendamustine, a chemotherapy drug used to treat certain types of cancer.
Used in Organic Synthesis:
In the field of organic chemistry, 5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester serves as a valuable building block for the synthesis of various complex organic molecules. Its unique structure allows for further functionalization and modification, making it a versatile component in the development of new pharmaceuticals and other chemical products.
Used in Research and Development:
5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester is also utilized in research and development settings, where it can be employed to study the properties and behavior of related benzimidazole derivatives. Understanding the chemical and biological activities of these compounds can lead to the discovery of new therapeutic agents and applications in various industries.

Upstream product

• 75-21-8 oxirane 
• 914626-62-3 1H-benzimidazol-1-methyl-5-amino-2-butanoic acid 
• 451459-95-3 5-(2-fluoro-5-nitroanilino)-5-oxopentanoic acid 
• 3543-73-5 ethyl 4‐(5‐amino‐1‐methyl‐1H‐benzo[d]imidazol‐2‐yl)butanoate 
• 540-51-2 2-bromoethanol 
• 31349-48-1 4-(1-methyl-5-nitro-1H-benzimidazol-2-yl)butanoic acid 
• 108-55-4 glutaric anhydride, 
• 369-36-8 6-fluoro-3-nitroaniline 
• 2784-94-3 4-bis(2'-hydroxy-ethyl)amino-1-methyl-amino-2-nitro-benzene 
• 29705-38-2 2,2'-[(4-fluoro-3-nitrophenyl)imino]bisethanol 
• 64-17-5 ethanol 
• 1464999-05-0 C₁₆H₂₅N₃O₅ 
• 157-18-6 oxirene 
• 3543-72-4 4‐(1‐methyl‐5‐nitro‐1H‐benzoimidazol‐2‐yl)butyric acid ethyl ester 

Downstream Products

• 16506-27-7 bendamustine 
• 3543-75-7 bendamustine hydrochloride 

Relevant articles and documents

Bendamustine hydrochloride preparation method suitable for industrial production

The invention provides a synthetic method of bendamustine hydrochloride. According to the synthetic method, residual thionyl chloride in a chlorination reaction is removed by using a proper solvent, and water is added for crystallization after part of reaction liquid is evaporated after a hydrolysis reaction is finished, so that the generation of impurities can be obviously reduced, the product purity is improved, and the product color is improved. By adopting the method disclosed by the invention, the pure white bendamustine hydrochloride product with the purity of 99.6% or above and the single impurity content of 0.3% or below can be prepared on a laboratory scale and a production scale without refining steps and decoloration operation, the purity of the product after re-crystallization and refining can reach 99.8% or below, the single impurity content is 0.1% or below, the quality requirements of national chemical bulk drugs are met, and qualified bulk drugs can be provided for research and production of bendamustine hydrochloride for injection. The method is mild in reaction condition, safe, simple and convenient to operate and suitable for industrial large-scale production.

PROCESS FOR BENDAMUSTINE HYDROCHLORIDE

The present invention provides a process for the preparation of 1H-benzimidazol-1-methyl-5-N,N-di(2-hydroxyethyl)-2-butanoic acid ethyl ester. The present invention also provides a process for the preparation of bendamustine hydrochloride. The present invention further provides a process for the purification of bendamustine hydrochloride.

PROCESS FOR THE PREPARATION OF BENDAMUSTINE

The present invention relates to a method for preparation of alkyl 4-[5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl]butanoate (7) from 2-fluoro-5-nitroaniline, comprising the steps of: (a) conversion of 2-fluoro-5-nitroaniline to 5-(2-fluoro-5-nitroanilino)-5-oxopentanoic acid (1) using glutaric anhydride, conversion of compound (1) to methylammonium 5-[2-(methylamino)-5-nitroanilino]-5-oxopentanoate (2) using methylamine; conversion of compound (2) to 5-[2-(methylamino)-5-nitroanilino]-5-oxopentanoic acid (3) and condensation of compound (3) to 4-(1-methyl-5-nitro-1H-benzimidazol-2-yl)butanoic acid (4); (b) esterification of the product (4) of step a) to alkyl 4-(1-methyl-5-nitro1H-benzimidazol-2-yl)butanoate (5); (c) reduction of the product of step b) to alkyl 4-(5-amino-1-methyl-1H-benzimidazol-2-yl)butanoate (6), and (d) conversion of the product of step c) to alkyl 4-[5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl]butanoate (7)