97832-05-8

Basic information

• Product Name: Bendamustine
• Synonyms: 4-[5-[Bis(2-chloroethyl)amino]-1-methyl-benzimidazol-2-yl]butyric acid hydrochloride;Bendamustine
• CAS NO: 97832-05-8
• Molecular Formula: C16H21Cl2N3O2.HCl
• Molecular Weight: 394.72
• Product Categories: API
• Mol File: 97832-05-8.mol
• Article Data: 18

Chemical Properties

• Melting Point: 149-151°C
• Boiling Point: 585.2 °C at 760 mmHg
• Flash Point: 307.7 °C
• Appearance: /
• Vapor Pressure: 1.55E-14mmHg at 25°C
• CAS DataBase Reference: Bendamustine(CAS DataBase Reference)
• NIST Chemistry Reference: Bendamustine(97832-05-8)
• EPA Substance Registry System: Bendamustine(97832-05-8)

Safety Data

• Hazardous Substances Data: 97832-05-8(Hazardous Substances Data)

Usage

Uses

Bendamustine is an intermediate in the synthesis of Bendamustine 3-Hydroxyprop-2-yl Ester (B132550), which is an impurity of anticancer drug Bendamustine Hydrochloride (B132500).

Enzyme inhibitor

This nitrogen mustard and anticancer drug (FWfree-acid = 358.26 g/mol; CAS 16506-27-7), also known by its code name SDX-105, its trade names Treanda?, Treakisym?, Ribomustin?, and Levact?, as well as by its systematic name 4-[5-[bis (2-chloroethyl) amino]-1-methylbenzimidazol-2- yl]butanoic acid, is a relatively nonspecific DNA alkylating agent that causes intra- and inter-strand cross-links. Bendamustine is used in the treatment of chronic lymphocytic leukemia (CLL), Hodgkin’s disease, non- Hodgkin’s lymphoma, multiple myeloma and lung cancer. Pharmacokinetics: After intravenous infusion, >95% of the drug becomes protein-bound, mainly to albumin; however, only free bendamustine is active. Bendamustine is metabolized by liver cytochrome p450, and elimination (renal) is biphasic, with an initial half-life of 6–10 minutes and a terminal half-life of approximately 30 minutes.

InChI:InChI=1/C16H21Cl2N3O2.ClH/c1-20-14-6-5-12(21(9-7-17)10-8-18)11-13(14)19-15(20)3-2-4-16(22)23;/h5-6,11H,2-4,7-10H2,1H3,(H,22,23);1H

Upstream product

• 109882-31-7 4-{5-[bis-(2-hydroxyethyl)amino]-1-methyl-1H-benzoimidazol-2-yl}-butanoic acid methyl ester 
• 1313020-24-4 isopropyl 4-(5-bis(2-hydroxyethyl)amino-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate 
• 1313020-25-5 bendamustine isopropyl ester 
• 3543-74-6 4-{5-[bis-(2-hydroxyl-ethyl)-amino]-1-methyl-1H-benzoimidazol-2yl}-butyric acid ethyl ester 
• 109882-25-9 4-{5-[bis-(2-chloro-ethyl)amino]-1-methyl-1H-benzoimidazol-2-yl}butyric acid methyl ester 

Downstream Products

• 109882-26-0 4-(6-((2-chloroethyl)(2-hydroxyethyl)amino)-3-methylbenzimidazolyl(2))butyric acid hydrochloride 
• 109882-25-9 4-{5-[bis-(2-chloro-ethyl)amino]-1-methyl-1H-benzoimidazol-2-yl}butyric acid methyl ester 
• 1609623-12-2 4-{5-[bis-(2-chloro-ethyl)amino]-1-methyl-1H-benzoimidazol-2-yl}butyric acid cyclohexyl ester 
• 109882-30-6 4-<1-Methyl-5-benzimidazolyl-(2)>butansaeure 
• 109882-29-3 4-<1-Methyl-5-benzimidazolyl-(2)>butansaeure-hydrochlorid 

Relevant articles and documents

Discovery of a novel, efficient, and scalable route to bendamustine hydrochloride: The API in Treanda

Process Research and Development activities leading to a new and efficient route to bendamustine hydrochloride, 1, the active ingredient in Treanda, a treatment for blood cancers, are disclosed. Two key features of this new process include a one-pot hydrogenation/dehydration sequence to construct the benzimidazole moiety and a novel reductive alkylation using chloroacetic acid and borane to install the bischloroethyl side chain. The number of synthetic steps has been significantly reduced to five from the eight in the current commercial process. The overall yield has been improved from 12% to 45%. Additionally, this new route eliminates chloroform, ethylene oxide, and sodium sulfide. Scale-up of the new route has been successfully demonstrated to prepare kilogram quantities of bendamustine hydrochloride.

Purification method of bendamustine hydrochloride

The invention relates to a purification method for bendamustine hydrochloride. The purification method comprises the following steps: (1) adding an aqueous hydrochloric acid solution to a crude bendamustine hydrochloride product, carrying out stirring for dissolving, and adding active carbon for decolorization; (2) adding an inorganic alkali solution into a solution obtained in the step (1) to adjust the pH value of the solution to 1 to 4, and then carrying out cooling, recrystallizing and filtering to obtain a filter cake; and (3) leaching the filter cake obtained in the step (2), and carrying out drying to obtain bendamustine hydrochloride. By adopting the purification method, high-purity bendamustine hydrochloride can be obtained from the crude bendamustine hydrochloride product at lowtemperature and normal temperature, new impurities are prevented from being generated at high temperature, product purity is 99.8% or above, and the content of each single impurity is lower than 0.10%; and the method has the advantages of simple process, short period, refining yield of 90% or above, good product quality, capacity of meeting preparation requirements and suitability for industrial production.

Novel Solid Forms Of Bendamustine Hydrochloride

Novel solid forms of bendamustine hydrochloride are described, as well as methods of their preparation and use.