Process Development and Scale-Up for the Preparation of the 1-Methyl-quinazoline-2,4-dione Wnt Inhibitor SEN461

被引：12

作者：

Betti, Matteo ^{[1
]}

Genesio, Eva ^{[2
]}

Panico, Alessandro

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 | 2013年 / 17卷 / 08期

关键词：

DISEASE;

D O I：

10.1021/op400145w

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 Wnt inhibitor SEN461 1 is described herein. The optimized route consists of nine chemical steps. The intermediates are solids and were isolated by filtrations. Critical reactions steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, we developed a synthetic procedure for the preparation of multihundred gram quantities of the final product. A further process development for the phase 1 clinical batch campaign is reported.

引用

页码：1042 / 1051

页数：10

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