Desymmetrization of a Propane-1,3-diol to Introduce the Quaternary Chiral Center of an AMG 176 Drug Substance Intermediate

被引：1

作者：

Ananthoji, Padmini K. K. ^{[1
]}

Arunachalampillai, Athimoolam ^{[2
]}

Beaver, Matthew G. G. ^{[1
]}

Fang, Yuan-Qing ^{[1
]}

Hedley, Simon J. J. ^{[3
]}

Lucas, Brian S. S. ^{[4
]}

Tedrow, Jason S. S. ^{[3
]}

Faul, Margaret M. M. ^{[3
]}

机构：

[1] Amgen Inc, Proc Dev, 360 Binney St, Cambridge, MA 02142 USA

[2] Biocon Pk, Syngene Amgen Res & Dev Ctr, Plot 2&3,Bommasandra 4Phase,Jigni Link Rd, Bangalore 560099, India

[3] Amgen Inc, Proc Dev, One Amgen Ctr Dr, Thousand Oaks, CA 91320 USA

[4] Amgen Inc, Dept Therapeut Discovery, 1120 Vet Blvd, South San Francisco, CA 94080 USA

来源：

SYNTHESIS-STUTTGART | 2023年 / 55卷 / 15期

关键词：

AMG; 176; process development; desymmetrization; Evans-; PyBOX ligand; 1; 3-diol; HIGHLY ENANTIOSELECTIVE DESYMMETRIZATION; CATALYZED ASYMMETRIC DESYMMETRIZATION; COPPER(II) COMPLEXES; TERT-ALKYLAMINES; ACYL TRANSFER; DERIVATIVES; 1,3-DIOLS; ALCOHOLS; ALDOL; DIOLS;

D O I：

10.1055/a-1989-2633

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A chiral Cu(II)-PyBOX complex was prepared and utilized to accomplish desymmetrization of a 1,3-diol en route to AMG 176. An expedient synthesis of the racemic 1,3-diol is described, in addition to efforts for rapid optimization and subsequent kilogram-scale execution of the desymmetrization process to generate material for pre-clinical activities. An overview of the kilogram-scale synthesis of the Cu(II)-PyBOX complex is provided.

引用

页码：2397 / 2405

页数：9

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