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

Chemical Properties

Off-White to Light Tan Solid

Uses

[1-Methyl-5-bis(2’-hydroxyethyl)aminobenzimidazolyl-2]butanoic Acid Ethyl Ester_x000D_Bendamustine Related Impurity 1 (cas# 3543-74-6) is a compound useful in organic synthesis.

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 THE PREPARATION OF BENDAMUSTINE HYDROCHLORIDE

The present invention relates to an improved process for the synthesis of bendamustine, in particular, bendamustine hydrochloride of the formula (VI) and its intermediate 1-Methyl-5-[bis(2-chloroethyl)amino]-1H-benzimidazol-2-yl]lithium butanoate of formula (V), both having a purity of ≧99%, which is simple, convenient, economical, does not use hazardous chemicals and industrially viable.

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)