Discovery of a Novel, Efficient, and Scalable Route to Bendamustine Hydrochloride: The API in Treanda

被引：13

作者：

Chen, Jian ^{[1
]}

Przyuski, Katrin ^{[1
]}

Roemmele, Renee ^{[1
]}

Bakale, Roger P. ^{[1
]}

机构：

[1] Cephalon Inc, Worldwide Proc Res & Dev, Malvern, PA 19355 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2011年 / 15卷 / 05期

关键词：

VITRO ANTITUMOR-ACTIVITY; ENZYME PRODRUG THERAPY; SODIUM-BOROHYDRIDE; SELECTIVE REDUCTIONS; CARBOXYPEPTIDASE G2; CARBOXYLIC-ACIDS; AROMATIC-AMINES; NITRO-COMPOUNDS; N-METHYLATION; ALKYLATION;

D O I：

10.1021/op200176f

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

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.

引用

页码：1063 / 1072

页数：10

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