Transition metal-catalyzed couplings in process chemistry : case studies from the pharmaceutical industry / edited by Javier Magano and Joshua R. Dunetz.

Format:

Book

Contributor:

Magano, Javier.

Dunetz, Joshua R.

Language:

English

Subjects (All):

Organic compounds--Synthesis.

Organic compounds.

Metal catalysts.

Physical Description:

1 online resource (408 p.)

Edition:

1st ed.

Place of Publication:

Weinheim : Wiley-VCH, 2013.

Language Note:

English

Summary:

This one-stop reference source is the first on this new and exciting technology to focus on case studies of large-scale industrial applications, presenting the information and facts that are otherwise hard to find in the current literature.Authors from Pfizer, Merck, DSM, Novartis, Amgen, and Astra Zeneca, among others, use case studies to showcase project evolution from inception to early and late development, including commercial routes where applicable. Each case study details at least one transition metal-catalyzed cross-coupling step, with special emphasis on lessons learned

Contents:

Transition Metal-Catalyzed Couplings in Process Chemistry: Case Studies from the Pharmaceutical Industry; Contents; Foreword 1; Foreword 2; Foreword 3; List of Contributors; Introduction; List of Abbreviations; 1 Copper-Catalyzed Coupling for a Green Process; 1.1 Introduction; 1.2 Synthesis of Amino Acid 14; 1.2.1 Asymmetric Hydrogenation Approach; 1.2.2 Enzymatic Approaches; 1.3 Copper-Catalyzed Cyclization; 1.3.1 C-N Bond Formation; 1.3.2 INDAC (1) Synthesis; 1.4 Sustainability; 1.5 Summary; References; 2 Experiences with Negishi Couplings on Technical Scale in Early Development

2.1 Introduction 2.2 Synthesis of LBT613 via Pd-Catalyzed Negishi Coupling; 2.3 Elaboration of a Negishi Coupling in the Synthesis of PDE472; 2.4 Ni-Catalyzed Negishi Coupling with Catalytic Amounts of ZnCl2; 2.5 Conclusions; References; 3 Developing Palladium-Catalyzed Arylations of Carbonyl-Activated C-H Bonds; 3.1 Introduction; 3.2 Suzuki Approach to Side Chain Installation; 3.3 Arylation of Carbonyl-Activated C-H Bonds; 3.4 Pd Purging from API; 3.5 Conclusions; References; 4 Development of a Practical Synthesis of Naphthyridone p38 MAP Kinase Inhibitor MK-0913; 4.1 Introduction

4.2 Medicinal Chemistry Approach to 14.3 Results and Discussion; 4.3.1 ADC Route to 21; 4.3.2 Tandem Heck-Lactamization Route to 23; 4.3.3 Suzuki-Miyaura Coupling; 4.3.4 Preparation of Grignard 22 for Endgame Couplings; 4.3.5 Coupling of Organomagnesium 22 and Naphthyridones 19-21; 4.4 Conclusions; References; 5 Practical Synthesis of a Cathepsin S Inhibitor; 5.1 Introduction; 5.2 Synthetic Strategy; 5.3 Syntheses of Building Blocks; 5.4 Sonogashira Coupling and Initial Purification of 1; 5.5 Salt Selection; 5.6 Conclusions; References

6 C-N Coupling Chemistry as a Means to Achieve a Complicated Molecular Architecture: the AR-A2 Case Story 6.1 A Novel Chemical Entity; 6.2 Evaluation of Synthetic Pathways: Finding the Best Route; 6.3 Enabling C-N Coupling by Defining the Reaction Space; 6.3.1 First Experiences; 6.3.2 Setbacks and Problem Solutions; 6.3.3 Scoping Out Key Parameters for Best Reaction Performance; 6.3.4 Ligand Screening; 6.3.5 Finding the Best Base; 6.3.6 Optimizing the Ligand/Metal Ratio; 6.3.7 Temperature Effect; 6.3.8 Optimizing the Catalyst Loading; 6.4 From Synthesis to Process; 6.4.1 Demonstration on Scale

6.4.2 Environmental Performance 6.4.3 Impurity Tracking; 6.5 Concluding Remarks; References; 7 Process Development and Scale-up of PF-03941275, a Novel Antibiotic; 7.1 Introduction; 7.2 Medicinal Chemistry Synthesis of PF-03941275; 7.3 Synthesis of 5-Bromo-2,4-difluorobenzaldehyde (1); 7.4 Synthesis of Amine 3; 7.5 Miyaura Borylation Reaction; 7.6 Suzuki-Miyaura Coupling; 7.7 Barbituric Acid Coupling; 7.8 Chlorination and API Isolation; 7.9 Conclusions; References; 8 Development of a Practical Negishi Coupling Process for the Manufacturing of BILB 1941, an HCV Polymerase Inhibitor

8.1 Introduction and Background

Notes:

Description based upon print version of record.

Includes bibliographical references and index.

ISBN:

9783527658923

3527658920

9783527658909

3527658904

9783527658930

3527658939

OCLC:

851695364