Multistep synthesis

    In chemistry, a multistep synthesis is a chemical strategy for creating a chemical compound by using multiple chemical reactions to convert one set of starting materials into the desired final compound. This approach is often used when the desired compound cannot be synthesized in a single step or when it is more efficient to synthesize the compound through multiple steps. Multistep syntheses often involve several different types of chemical reactions, such as organic reactions, inorganic reactions, and polymerization reactions. By carefully planning the sequence of reactions, chemists can synthesize complex compounds in a controlled and efficient manner. Multistep syntheses are an important tool in the field of synthetic chemistry, as they allow chemists to create a wide range of compounds for a variety of applications.

    In flow chemistry, each step of the synthesis would be carried out in a separate flow reactor, with the reactants from one step being continuously flowed into the next reactor to undergo the next reaction in the sequence.

    Examples of published literature for Multistep synthesis

    Scale-up and Optimization of a Continuous Flow Synthesis of an α-Thio-β-chloroacrylamide

    Olga C. Dennehy1, Denis Lynch1, Stuart G. Collins1*, Anita R. Maguire2*, Humphrey A. Moynihan1*

    • 1School of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork T12 K8AF, Ireland.
    • 2School of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork T12 K8AF, Ireland
    View abstract

    In-Line Purification: A Key Component to Facilitate Drug Synthesis and Process Development in Medicinal Chemistry

    Nopphon Weeranoppanant1, 2, Andrea Adamo3

    • 1Department of Chemical Engineering, Faculty of Engineering, Burapha University, 169 Longhard Bangsaen Road, Muang, Chonburi 02131, Thailand
    • 2School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Wangchan Valley 555 Moo 1 Payupnai, Wangchan, Rayong 21210 Thailand
    • 3Zaiput Flow Technologies, 300 Second Avenue, Waltham, Massachusetts 02451, United States
    View abstract

    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-Rentsch1,2, 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. Honea, Alistair Boydb, Anne O’Kearney-McMullanb, Richard A. Bournea*, Frans L. Mullera*

    • 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. Damiãoa, Renan Galavernaa, Alan P. Kozikowskib, James Eubanksc, Julio C. Pastrea

    • 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 Battilocchioa*, Francesco Bosicaa, Sam M. Rowea, Bruna L. Abreua, Edouard Godineaub*, Matthias Lehmannb, Steven V. Leya

    • 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. Shukla1,2, Amol A. Kulkarni1,2

    • 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 Oelgemöller2 *

    • 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 Yousufa, Andrew K. Richardsb, Andrew N. Dwyerc, Bruno Linclaua, 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. Seeberger1 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 McQuade1 3, Peter H. Seeberger1 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 Battilocchio1,3, 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 Martinelli1*

    • 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. Holmes1,2, 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

    Application Notes regarding Multistep synthesis

    No related applications found.

    Get in touch

    For more information on flow chemistry systems and services please use the contact methods below.

    Call us on +44 (0)1284 728659 or Email us