Multistep synthesis

Synthetic Route Design of AZD4635, an A2AR Antagonist

Mairi M. Littleson ^*†, Andrew D. Campbell ^†, Adam Clarke ^†, Mark Dow ^†, Gareth Ensor ^†, Matthew C. Evans ^†, Adam Herring ^†,Bethany A. Jackson ^†, Lucinda V. Jackson ^†, Staffan Karlsson ^‡, David J. Klauber ^†, Danny H. Legg ^§, Kevin W. Leslie ^†, Štefan Moravcí̌k ^‡, Chris D. Parsons ^§, Thomas O. Ronson ^†, Rebecca E. Meadows ^†

• ^† Chemical Development, Pharmaceutical Technology and Development, AstraZeneca, Macclesfield Campus, SK10 2NA, Macclesfield, U.K.
• ^‡ Early Chemical Development, Pharmaceutical Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, SE-431 83 Mölndal, Sweden
• ^§ Early Chemical Development, Pharmaceutical Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield Campus, SK10 2NA, Macclesfield, U.K.

View abstract

A Novel and Efficient Continuous-Flow Route To Prepare Trifluoromethylated N‑Fused Heterocycles for Drug Discovery and Pharmaceutical Manufacturing

Lara Amini-Rentsch^1,2, Ennio Vanoli², Sylvia Richard-Bildstein¹, Roger Marti², Gianvito Vilé¹

• ¹ Idorsia Pharmaceuticals Ltd., Chemistry Technologies & Lead Discovery, Department of Drug Discovery Chemistry, Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland
• ² University of Applied Sciences Western Switzerland (HES-SO), Haute Ecole d’Ingénierie et d’Architecture de Fribourg, Institute of Chemical Technology, 80 boulevard de Pérolles, CH-1700 Fribourg, Switzerland

View abstract

Definitive screening designs for multistep kinetic models in flow

Christopher A. Hone^a, Alistair Boyd^b, Anne O’Kearney-McMullan^b, Richard A. Bourne^a*, Frans L. Muller^a*

• ^a Institute of Process Research and Development (iPRD), School of Chemistry and School of Chemical and Process Engineering, University of Leeds, LS2 9JT, UK
• ^b Global Development, AstraZeneca, Macclesfield, Cheshire, UK, SK10 2NA, UK

View abstract

Continuous Flow Synthesis of Highly Substituted Tetrahydrofurans

Patrick Hoffmeyer, Christoph Schneider

• Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, D, ‐04103 Leipzig Germany

View abstract

A Consolidated and Continuous Synthesis of Ciprofloxacin from a Vinylogous Cyclopropyl Amide

N. Perrer Tosso, Bimbisar K. Desai, Eliseu De Oliveira, Juekun Wen, John Tomlin, and B. Frank Gupton*

• Department of Chemistry and Department of Chemical and Life Science Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, Virginia 23220, United States

View abstract

A Continuous Flow Strategy for the Facile Synthesis and Elaboration of Semi‐Saturated Heterobicyclic Fragments

Nicola Luise, Eleanor Wyatt, Gary Tarver, Paul Graham Wyatt

• University of Dundee, School of Life Sciences, DD1 5EH Dundee, UNITED KINGDOM

View abstract

Using Carbon Dioxide as a Building Block in Continuous Flow Synthesis

Hyowon Seo, Long V. Nguyen, Timothy F. Jamison

• Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts

View abstract

A Convergent Continuous Multistep Process for the Preparation of C4-Oxime-Substituted Thiazoles

Edouard Godineau ^*†, Claudio Battilocchio ^†‡, Matthias Lehmann ^†, Steven V. Ley ^†, Ricardo Labes ^‡, Letitia Birnoschi ^‡, Srinivas Subramanian ^§, C.S Prasanna ^§ , Amol Gorde ^§, Mahesh Kalbagh ^§, Vivek Khade ^§, Anton Scherrer ^†, Anthony C. O’Sullivan ^†

• ^† Syngenta Crop Protection, Process Research, Schaffhauserstrasse 101, CH-4332, Switzerland
• ^‡ Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, UK
• ^§ Syngenta Research and Technology Centre, Santa Monica Works, Corlim, Goa India, 403110

View abstract

Multistep Continuous-Flow Processes for the Preparation of Heterocyclic Active Pharmaceutical Ingredients

Romaric Gérardy, Jean-Christophe M. Monbaliu

• Center for Integrated Technology and Organic Synthesis, Department of Chemistry, University of Liège, Liège, Belgium

View abstract

A combination of flow and batch mode processes for the efficient preparation of mGlu2/3 receptor negative allosteric modulators (NAMs)

Raveendra Panickar Dhanya, Ananda Herath, Douglas J. Sheffler, Nicholas D.P. Cosford

• Cancer Metabolism and Signaling Networks Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA

View abstract

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

Marcus Baumann, Ian R. Baxendale and Fabien Deplante

• Department of Chemistry, University of Durham, South Road, Durham, Durham, DH1 3LE, UK

View abstract

Sustainable flow synthesis of a versatile cyclopentenone building block

Marcus Baumann^†, Ian R. Baxendale^†, Paolo Filipponi^‡, Te Hu^†

• ^† Department of Chemistry, University of Durham, South Road, DH1 3LE Durham, U.K
• ^‡ Novartis Pharma AG, Fabrikstrasse 14, 4002 Basel, Switzerland

View abstract

Telescoped continuous flow generation of a library of highly substituted 3-thio-1,2,4-triazoles.

Mariana C. F. C. B. Damião^a, Renan Galaverna^a, Alan P. Kozikowski^b, James Eubanks^c, Julio C. Pastre^a

• ^a Institute of Chemistry, University of Campinas - UNICAMP, PO Box 6154 - Zip Code 13083-970, Campinas, SP, Brazil
• ^b StarWise Therapeutics LLC - University Research Park – Zip Code 53719-1235, Madison, Wisconsin, USA
• ^c Division of Genetics and Development - Krembil Research Institute – Zip Code M5T 2S8, Toronto, Ontario, Canada

View abstract

Continuous preparation and use of dibromoformaldoxime as a reactive intermediate for the synthesis of 3- bromoisoxazolines

Claudio Battilocchio^a*, Francesco Bosica^a, Sam M. Rowe^a, Bruna L. Abreu^a, Edouard Godineau^b*, Matthias Lehmann^b, Steven V. Ley^a

• ^a Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.
• ^b Syngenta Crop Protection AG, Crop Protection Research, Schaffhauserstrasse 101, CH-4332 Stein, Switzerland

View abstract

Flow assisted synthesis: a key fragment of SR 142948A

Matthew Oliver Kitching, Olivia E Dixon, Marcus Baumann, Ian Richard Baxendale

• University of Durham, Chemistry, Durham, UK

View abstract

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

Chinmay A. Shukla^1,2, Amol A. Kulkarni^1,2

• ¹ Academy of Scientific and Innovative Research (AcSIR), CSIR-National Chemical Laboratory (NCL) Campus, Pune 411008, India
• ² Chem. Eng. & Proc. Dev. Div., CSIR-National Chemical Laboratory, Dr. Homi Bhaba Road, Pashan, Pune 411008, India

View abstract

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

Ananda Herath, Nicholas D. P. Cosford

• Cancer Metabolism & Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA

View abstract

Photodecarboxylations in an advanced meso-scale continuous flow photoreactor

Sam Josland¹, Saira Mumtaz², Michael Oelgemöller^{2 *}

• ¹ University of Southampton, Department of Chemistry, University Road, Southampton, SO17 1BJ, United Kingdom
• ² James Cook University, College of Science, Technology and Engineering, Townsville, QLD 4811, Australia

View abstract

A Short Multi-step Flow Synthesis of a Potential Spirocyclic Fragrance Component

Ian R. Baxendale*

• Department of Chemistry, University of Durham, South Road, Durham, DH1 3LE, UK

View abstract

The development of a short route to the API ropinirole hydrochloride

Zeshan Yousuf^a, Andrew K. Richards^b, Andrew N. Dwyer^c, Bruno Linclau^a, David C. Harrowven^{* a}

• ^a Chemistry, University of Southampton, Highfield, Southampton, UK
• ^b GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, UK
• ^c Formally at GlaxoSmithKline Innovation and Sustainable Manufacturing COE, Worthing, UK

View abstract

Chemical Assembly Systems: Layered Control for Divergent, Continuous, Multistep Syntheses of Active Pharmaceutical Ingredients

Dr. Diego Ghislieri, Dr. Kerry Gilmore, Prof. Dr. Peter H. Seeberger^*

• Department of Biomolecular Systems, Max-Planck Institute for Colloids and Interfaces, Universität Berlin, Germany

View abstract

A Concise Flow Synthesis of Efavirenz

Dr. Camille A. Correia¹, Dr. Kerry Gilmore¹, Prof. Dr. D. Tyler McQuade³, Prof. Dr. Peter H. Seeberger^{1 2 *}

• ¹ Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam (Germany)
• ² Institute for Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin (Germany)
• ³ Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306 (USA)

View abstract

Flow synthesis of organic azides and the multistep synthesis of imines and amines using a new monolithic triphenylphosphine reagent

Catherine J. Smith, Christopher D. Smith, Nikzad Nikbin, Steven V. Ley, Ian R. Baxendale

• Innovative Technology Centre, Cambridge, UK

View abstract

Multistep Flow Synthesis of 5-Amino-2-aryl-2H-[1,2,3]-triazole-4-carbonitriles

YDr. Jérôme Jacq, Dr. Patrick Pasau^*

• UCB Biopharma, Avenue de l'Industrie, 1420 Braine l'Alleud (Belgium)

View abstract

Continuous Flow Synthesis of Thieno[2,3-c]isoquinolin-5(4H)-one Scaffold: A Valuable Source of PARP-1 Inhibitors

Paolo Filipponi^†, Carmine Ostacolo^‡, Ettore Novellino^‡, Roberto Pellicciari^†§, Antimo Gioiello^*†

• ^†Dipartimento di Scienze Farmaceutiche, Università di Perugia, Via del Liceo 1, I-06123 Perugia, Italy
• ^‡Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Napoli, Italy §TES Pharma S.r.l., Corciano (Perugia), Italy

View abstract

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

Richard J. Ingham¹, Claudio Battilocchio¹, Joel M. Hawkins², Steven V. Ley¹

• ¹ Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK
• ² Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA

View abstract

Applying Flow Chemistry: Methods, Materials, and Multistep Synthesis

D. Tyler McQuade^{1 3}, Peter H. Seeberger^{1 2}

• ¹ Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces
• ² Institute for Chemistry and Biochemistry, Freie Universität Berlin,
• ³ Department of Chemistry and Biochemistry, Florida State University

View abstract

Synthesis of RAFT Block Copolymers in a Multi-Stage Continuous Flow Process Inside a Tubular Reactor

Christian H. Hornung, Xuan Nguyen, Stella Kyi, John Chiefari, Simon Saubern

• CSIRO Materials Science & Engineering, Victoria, Australia.

View abstract

An expeditious synthesis of imatinib and analogues utilising flow chemistry methods

Mark D Hopkin, Ian Baxendale, Steven.V.Ley

• Dept of Chemistry, University of Cambridge, UK

View abstract

A Multi-Step Continuous Flow Process for the N-Demethylation of Alkaloids

Yuji Nakano¹, G. Paul Savage¹, Simon Saubern¹, Peter J. Scammells², Anastasios Polyzos¹

• ¹ CSIRO Materials Science and Engineering, Victoria, Australia.
• ² Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria, Australia.

View abstract

A Two-Stage Continuous-Flow Synthesis of Spirooxazine Photochromic Dyes

Mark York¹²³, Adriana Edenharter¹

• ¹CSIRO Materials Science and Engineering, Clayton, Vic. 3169, Australia.
• ²Cooperative Research Centre for Polymers, Notting Hill, Vic. 3168, Australia.
• ³Advanced Polymerik Pty Ltd, Notting Hill, Vic. 3168, Australia.

View abstract

Synthesis of an H3 Antagonist via Sequential One-Pot Additions of a Magnesium Ate Complex and an Amine to a 1,4-Ketoester followed by Carbonyl-Directed Fluoride Addition

Joel M. Hawkins, Pascal Dubé, Mark T. Maloney, Lulin Wei. Marcus Ewing, Stephen M. Chesnut, Joshua R. Denette, Brett M. Lillie, Rajappa Vaidyanathan

• Pharmaceutical Sciences, Pfizer Inc., Groton, USA

View abstract

Scale-Up of Flow-Assisted Synthesis of C2-Symmetric Chiral PyBox Ligands

Claudio Battilocchio^1,3, Marcus Baumann¹, Ian R. Baxendale¹, Mariangela Biava³, Matthew O. Kitching¹, Steven V. Ley¹, Rainer E. Martin^*2, Stephan A. Ohnmacht², Nicholas D. C. Tappin¹

• ¹Department of Chemistry, University of Cambridge, UK
• ²F. Hoffmann-La Roche Ltd., Pharmaceuticals Division, Basel, Switzerland
• ³Department of Pharmaceutical Chemistry and Technology, Sapienza University of Rome, Italy

View abstract

Synthesis of a Drug-Like Focused Library of Trisubstituted Pyrrolidines Using Integrated Flow Chemistry and Batch Methods

Marcus Baumann¹, Ian R. Baxendale¹, Steven V. Ley¹, Christoph Kuratli², Rainer E. Martin², Josef Schneider²

• ¹Innovative Technology Centre, University of Cambridge, U.K.
• ²F. Hoffmann-La Roche Ltd., Basel, Switzerland

View abstract

Synthesis of (+)-Dumetorine and Congeners by Using Flow Chemistry Technologies

Elena Riva², Anna Rencurosi¹, Stefania Gagliardi¹, Daniele Passarella², Marisa Martinelli^1*

• ¹NiKem Research S.r.l., Milan, Italy
• ²Università degli Studi di Milano,Milan, Italy

View abstract

Preparation of fluoxetine by multiple flow processing steps

Batoul Ahmed-Omer, Adam J. Sanderson

• Eli Lilly and Co. Ltd.
• Lilly Research Centre, UK.

View abstract

Diastereoselective Chain-Elongation Reactions Using Microreactors for Applications in Complex Molecule Assembly

Catherine F. Carter¹, Heiko Lange¹, Daiki Sakai², Ian R. Baxendale¹, Steven V. Ley¹

• ¹Innovative Technology Centre, University of Cambridge, UK, CB2 1EW, UK
• ²Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan

View abstract

A fully automated, multistep flow synthesis of 5-amino-4-cyano-1,2,3-triazoles

Catherine J. Smith, Nikzad Nikbin, Steven V. Ley, Heiko Lange, Ian R. Baxendale

• Innovative Technology Centre, Cambridge, UK

View abstract

A breakthrough method for the accurate addition of reagents in multi-step segmented flow processing

Heiko Lange¹, Catherine F. Carter¹, Mark D. Hopkin¹, Adrian Burke², Jon G. Goode², Ian R. Baxendale¹, Steven V. Ley¹

• ¹Innovative Technology Centre, University of Cambridge, UK
• ²Mettler-Toledo AutoChem UK

View abstract

One-Flow, Multistep Synthesis of Nucleosides by Brønsted Acid-Catalyzed Glycosylation

Adam Sniady, Matthew W. Bedore, Timothy F. Jamison

• Novartis Institutes for Biomedical Research Inc., Cambridge, USA MIT, Cambridge, USA

View abstract

Safe and Reliable Synthesis of Diazoketones and Quinoxalines in a Continuous Flow Reactor

Laetitia J. Martin¹, Andreas L. Marzinzik¹, Steven V. Ley², Ian R. Baxendale²

• ¹Novartis Institute for BioMedical Research, Basel, Switzerland
• ²Innovative Technology Centre, Department of Chemistry, University of Cambridge

View abstract

Preparation of arylsulfonyl chlorides by chlorosulfonylation of in situ generated diazonium salts using a continuous flow reactor

Laia Malet-Sanz, Julia Madrzak, Steven V.Ley, Ian R.Baxendale

• Innovative Technology Centre, University of Cambridge

View abstract

Synthesis of Highly Substituted Nitropyrrolidines, Nitropyrrolizines and Nitropyrroles via Multicomponent-Multistep Sequences within a Flow Reactor

Marcus Baumann, Ian R. Baxendale, Andreas Kirschning, Steven V. Ley^*, Jens Wegner

• Department of Chemistry, University of Cambridge

View abstract

Flow synthesis of tricyclic spiropiperidines as building blocks for the histrionicotoxin family of alkaloids

Malte Brasholz¹, Brian A. Johnson², James M. Macdonald¹, Anastasios Polyzos¹, John Tsanaktsidis¹, Simon Saubern¹, Andrew B. Holmes^1,2, John H. Ryan¹

• ¹CSIRO Molecular and Health Technologies, Victoria, Australia
• ²School of Chemistry, Bio 21 Institute, University of Melbourne, Victoria, Australia

View abstract

The application of flow microreactors to the preparation of a family of casein kinase I inhibitors

Francesco Venturoni, Nikzad Nikbin, Steven V. Ley, Ian R. Baxendale

• Innovative Technology Centre, Department of Chemistry, University of Cambridge

View abstract

A highly efficient flow reactor process for the synthesis of N-Boc-3,4-dehydro-l-proline methyl ester

Lucia Tamborini, Paola Conti, Andrea Pinto, Carlo De Micheli

• Dipartimento di Scienze Farmaceutiche ‘Pietro Pratesi’,
• Università degli Studi di Milano, Italy

View abstract

Multi-Step Synthesis by Using Modular Flow Reactors: The Preparation of YneOnes and Their Use in Heterocycle Synthesis

Ian R. Baxendale¹, Søren C. Schou², Jörg Sedelmeier¹, Steven V. Ley¹

• ¹ITC, Department of Chemistry, University of Cambridge
• ²LEO Pharma, Medicinal Chemistry Research, Denmark

View abstract

Multistep Synthesis Using Modular Flow Reactors: Bestmann-Ohira Reagent for the Formation of Alkynes and Triazoles

Ian R. Baxendale¹, Steven V. Ley¹, Andrew C. Mansfield², Christopher D. Smith¹

• ¹ITC, Department of Chemistry, University of Cambridge,
• ²Pfizer Global R&D Research Centre, Sandwich, (UK)

View abstract

Efficient Continuous Flow Synthesis of Hydroxamic Acids and Suberoylanilide Hydroxamic Acid Preparation

E. Riva¹, S. Gagliardi², Caterina Mazzoni², M. Martinelli², D. Passarella¹, D. Vigo², A. Rencurosi²

• ¹Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Italy
• ²NiKem Research S.r.l., Milan, Italy

View abstract

Tagged phosphine reagents to assist reaction work-up by phase-switched scavenging using a modular flow reactor

Christopher D. Smith, Ian Baxendale, Geoffrey Tranmer, Marcus Baumann, Stephen Smith, Russell Lewthwaite, Steven V. Ley

• Department of Chemistry, University of Cambridge, UK

View abstract

A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine: a new paradigm for molecular assembly

Ian R. Baxendale, Jon Deeley, Charlotte M. Griffiths-Jones, Steven V. Ley, Steen Saaby, Geoffrey K. Tranmer

• Innovative Technology Centre, University of Cambridge

View abstract