A Scalable Route to the SMO Receptor Antagonist SEN826: Benzimidazole Synthesis via Enhanced in Situ Formation of the Bisulfite-Aldehyde Complex

被引：22

作者：

Betti, Matteo ^{[1
]}

Genesio, Eva ^{[2
]}

Marconi, Guido

Coccone, Salvatore Sanna

Wiedenau, Paul

机构：

[1] Siena Biotech SpA, Proc Chem Unit, I-53100 Siena, Italy

[2] Siena Biotech SpA, Compound Management & Anal Unit, I-53100 Siena, Italy

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2014年 / 18卷 / 06期

关键词：

CATALYZED AMINATION; ARYL; ANALOGS; CANCER; ESTERS;

D O I：

10.1021/op4002092

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A practical and scalable route to the SMO antagonist SEN826 1 is described herein, including the discussion of an alternative approach to the synthesis of the target molecule. The optimized route consists of five chemical steps. A new and efficient access to the key intermediate 6 via the bisulfite-aldehyde complex was developed, significantly enhancing the yields and reducing costs. As a result, a synthetic procedure for preparation of multihundred gram quantities of the final product has been developed.

引用

页码：699 / 708

页数：10

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