Development of a Scalable Route to a Dual NK-1/Serotonin Receptor Antagonist

被引：27

作者：

Risatti, Christina ^{[1
]}

Natalie, Kenneth J., Jr. ^{[1
]}

Shi, Zhongping ^{[1
]}

Conlon, David A. ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Chem Dev, Res & Dev, New Brunswick, NJ 08903 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2013年 / 17卷 / 02期

关键词：

SEROTONIN REUPTAKE INHIBITORS; CROSS-COUPLING REACTIONS; NK1; ANTAGONISTS; SUBSTANCE-P; TRICHLOROISOCYANURIC ACID; POTENTIAL ANTIDEPRESSANTS; HETEROCYCLIC-COMPOUNDS; PYRIDINE-DERIVATIVES; EFFICIENT SYNTHESIS; GRIGNARD-REAGENTS;

D O I：

10.1021/op300323k

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

The evolution of a process for the preparation of a new heterocyclic dual NK1/serotonin receptor antagonist is described. The final synthesis features a telescoped sequence in which an iron(III)-catalyzed Grignard coupling is followed by a benzylic chlorination utilizing trichlorocyanuric acid to construct an unsymmetrical 2,4,6-trisubstituted pyridine. Etherification of a 4,4'-arylhydroxymethane substituted piperidine fragment completes the synthesis of the active pharmaceutical ingredient in 44% overall yield.

引用

页码：257 / 264

页数：8

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