Merck chemistry: Discovery and small molecule process research & development

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“ We try never to forget that medicine is for the people. It is not for the profits.”

— George W. Merck

Great medicines change the world. Great minds make them possible.

In Discovery Chemistry, we strive to invent medicines that save and improve lives of people around the world. Our responsibility is to constantly seek better ways to achieve this mission and, as a result, our strategy in Discovery Chemistry is changing in exciting ways. At our core, we have outstanding synthetic and medicinal chemists who employ or invent cutting-edge methodologies that enable the best designs for drug-like molecules to be synthesized without limitation. Our scope in Discovery Chemistry has widened, and we are now inventing potential new medicines not only in the small molecule modality but also in peptides, oligonucleotides, degraders, and conjugates. Across these modalities, we are seeking to accelerate the rate of discovery by expanding our use of automation, machine learning-enabled predictive tools, structural chemistry, and other new technology platforms. Most importantly, we recognize that diverse skill sets and backgrounds make for the best teams, and we are growing an inclusive culture in which everyone feels they belong, can have tremendous impact, and are able to continuously learn and grow. We believe the rapid expansion of biological data and insight into human disease will only increase our opportunities to achieve our mission, and we’re transforming Discovery Chemistry to take full advantage of it.

Rob Garbaccio VP, Discovery Chemistry

Kevin Campos AVP, Small Molecule Process Research & Development

At Merck, when we embark on the development of a commercial manufacturing process for a promising drug candidate, we strive to design the most direct method to convert commodity chemicals into the target molecule with zero waste. Inevitably, the transformations that we imagine do not exist, and we foster a mentality that thinks creatively to strategically invent novel synthetic methods to achieve this aspirational goal. Merck’s investment in this mindset of innovation provides countless benefits to how our medicines are manufactured, minimizing the environmental impact of our processes, maximizing access to our medicines for patients worldwide, and influencing the field of synthetic chemistry as we do it.

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Target identification and validation

Chemical Biology

Discovery Chemistry

Discovery Process Chemistry

Process Chemistry

Drug discovery and preclinical studies

Early developmentPhase I, phase II

Late developmentPhase III, commercialization

Enabling technologies & external capabilitiesDrug discovery and development at Merck: Inventing for life

Our mission is to discover, develop, and deliver innovative products and services that save and improve lives around the world.

We are committed to being the premier research-intensive biopharmaceutical company.

• Bringing innovation to patients and physicians• Investing in key areas to address unmet needs• Accessing the best external science

Synthetic chemistry impacts all stages of drug discovery and developmentChemistry at Merck offers opportunities to conduct research across all phases of drug development, from the preclinical stage to commercialization. Although our primary focus is on the discovery and development of small molecule therapeutics, we

also strive to invent and deploy new technologies to impact both chemical and biochemical matter as well as new therapies at the intersection of biology and chemistry.

Invent the best molecules for future Merck products

Supply API to accelerate program development

Deliver the best science at first filing

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Explore chemistry at Merck

We recruit talented chemists to work closely with colleagues across multiple functional areas.

Process Chemistry

Discovery Chemistry

Discovery Process Chemistry

Chemical Biology

Enabling Technologies

External capabilities

• Solve complex chemical problems by inventing cutting-edge synthetic methods and applying them to commercial routes

• Work with a number of partner groups to achieve “best science at first filing”

• Design and synthesize compounds to advance the best molecules as new drug candidates, regardless of modality (small molecules, peptides, oligonucleotides, etc.)

• Develop synthetic routes and methods to enable rapid advancement of novel chemical matter

• Interface between Process Chemistry and Discovery Chemistry

• Invent and deploy novel synthetic technology to accelerate drug discovery and inform future drug development

• Design and synthesize tool compounds for use in elucidating novel drug targets and molecular mechanisms of action

• Explore new ways of using chemistry to interrogate biology

Invent cutting-edge technologies to support our pipeline with the following:• Data-rich

experimentation• Reaction engineering• Particle engineering

• Biocatalysis• Chemocatalysis• Flow chemistry• Automation

• Support Merck’s pipeline by interfacing with external partners and coordinating with internal chemistry

• Oversee external partners to ensure successful deliveries of drug candidates and drug substance for clinical trials

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Select recent publications #MerckChemistryMerck’s commitment to scientific excellence

Award-winning scientists2021 DOC Young Investigators: Raphaëlle Berger, Amélie Dion, Feng Peng, Steve Silverman

2020 DOC Young Investigators: Anna Fryszkowska, Christopher Plummer

2021 Peter J. Dunn Awardees: Cecilia Bottecchia, Stephen Dalby, François Lévesque, Jonathan McMullen

2020 WCC Rising Stars: Yeon-Hee Lim, Dani Schultz

2021 MEDI Young Investigator: Donna Hayes

2020 MEDI Young Investigator: Jackie Hicks

2021 Technical Achievement: Jeff Schubert

2020 Technical Achievement: Helen Chen

2020 ACS Fellow: Rebecca Ruck

And award-winning science2017 ACS Heroes of Chemistry

Merck 2017 Heroes of Chemistry video capture

Heroes of Chemistry is an annual award sponsored by the American Chemical Society that recognizes talented industrial chemical scientists whose work has led to the development of successful commercialized products ingrained with chemistry for the benefit of humankind.

(elbasvir and grazoprevir) tablets

C(sp3)-H Methylation Enabled by Peroxide Photosensitization and Ni-Mediated Radical Coupling. Science 2021, 372, 398.

Microenvironment mapping via Dexter energy transfer on immune cells. Science 2020, 367, 1091.

Design of an in vitro biocatalytic cascade for the manufacture of islatravir. Science 2019, 366, 6470.

Pharmaceutical diversification via palladium oxidative addition complexes. Science 2019, 363, 405.

Photon Equivalents as a Parameter for Scaling Photoredox Reactions in Flow: Translation of Photocatalytic C−N Cross‐Coupling from Lab Scale to Multikilogram Scale. Angew. Chem. Int. Ed. 2020, 59, 11964.

The Discovery of Two Novel Classes of 5,5-Bicyclic Nucleoside-Derived PRMT5 Inhibitors for the Treatment of Cancer. J. Med. Chem. 2021, 64, 3911.

A Metallaphotoredox Method for the Expansion of Benzyl SAR on Electron-Deficient Amines. Org. Lett. 2020, 22, 1052.

New Mechanism for Cinchona Alkaloid-Catalysis Allows for an Efficient Thiophosphorylation Reaction. J. Am. Chem. Soc. 2020, 142, 20021.

The Merger of Decatungstate and Copper Catalysis to Enable Aliphatic C(sp3)–H Trifluoromethylation. Nat. Chem. 2020, 12, 459.

A Multifunctional Reagent Designed for the Site-Selective Amination of Pyridines. J. Am. Chem. Soc. 2020, 142, 8614.

Reductive Cleavage of Secondary Sulfonamides: Converting Terminal Functional Groups into Versatile Synthetic Handles. J. Am. Chem. Soc. 2019, 141, 18416.

Continuous Flow-Enabled Synthesis of Bench-Stable Bicyclo[1.1.1]pentane Trifluoroborate Salts and Their Utilization in Metallaphotoredox Cross-Couplings. Org. Lett. 2020, 22, 1648.

Discovery of MK-8719, a Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies. J. Med. Chem. 2019, 62, 10062.

Electrochemical Synthesis of Hindered Primary and Secondary Amines via Proton-Coupled Electron Transfer. J. Am. Chem. Soc. 2020, 142, 468.

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Merck’s commitment to the next generation of scientistsMerck’s commitment to sustainability

EPA Green Chemistry ChallengeThe Green Chemistry Challenge Awards promote the environmental and economic benefits of developing and using novel green chemistry. These prestigious annual awards recognize chemical technologies that incorporate the principles of green chemistry into chemical design, manufacture, and use.

Gefapixant 2021

2018

Uprifosbuvir 2020

2017

2019

2010

Women Chemists Committee Merck Research Award• Receive a $1,500 stipend to cover Fall ACS national meeting expenses• Present their research at a WCC/Merck half-day symposium• Be recognized at the awards symposium and the WCC luncheon • Network with other WCC/Merck scientists

Underrepresented Chemists of Color Award• Networking opportunities with other winners and Merck scientists;

matched with a Merck mentor• Travel expenses, meals, and accommodation are covered for the award

symposium at the Merck Rahway site• Eligible to third-year graduate students through postdocs conducting

chemistry research at a U.S. institution• For more information, please email chemistsofcolor@merck.com

MRL Postdoc Program• Program launched in 2012

• Around 60 postdocs at any time, across all Merck sites• 30-36 new postdocs added each year

• Original research projects in Merck Labs• Objective is high-profile publications and presentations by the postdoc

• Provides immersion for the postdoc in collaborative industrial research teams with an academic focus in a commercial environment

2021 WCC Merck research awardees Merck mentors

Green Ahn, Stanford Frances Rodriquez-Riera Stanna Dorn, Indiana University, Bloomington Cindy Hong Morgan Gibbs, UNC, Chapel Hill Valerie ShurtleffBeryl Li, Princeton Jenny ObligacionNandhini Rajagopal, Syracuse Libby HennessyAlexa Torelli, University of Toronto Marion EmmertDaisy Unsihuay, Purdue Anisha PatelVictoria Yan, UT MD Anderson Cancer Center Samantha Shockley

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On Forbes list of America’s Best Employers for Diversity 2020

Strong career paths and cutting-edge science draw more women to our small molecule process R&D team

ACS National historic chemical landmarks

The vitamin B complexMerck scientists responsible for the industrial synthesis of the vitamin B complex in the 1930s and 1940s

Become a part of Merck’s rich history… By being a part of Merck’s diverse and inclusive future

Our company’s Employee Business Resource Groups (EBRGs) were awarded the Above and Beyond Award by Diversity Best Practices, a division of Working Mother Media, for the groups’ significant and measurable impact on corporate culture, business results, and society.

Discovery of ivermectinMerck scientist William C. Campbell receiving his 2015 Nobel Prize in Physiology or Medicine for the discovery of, and work on, ivermectin in the 1970s and 1980s

CAPABILITYNETWORK

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Our commitment to you

Our people are critical to our mission of improving and saving lives around the world. The work we do sparks and channels creative energy that turns potential into fulfillment, moving toward tomorrow’s solutions in an endless cycle: from invention, to impact, to inspiration — and to the next invention.

At Merck, we are committed to:• Recognizing your unique skill set and nurturing your talent• Developing a career path reflective of your scientific interests• Ensuring diversity and inclusion at every level of our organization• Maintaining a culture that supports work/life balance

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Where are we located?

Rahway, New JerseyOur Rahway, NJ site is significant for its deep legacy in drug discovery and manufacturing. It is currently home to Process Chemistry, Discovery Process Chemistry, and Enabling Technologies. Our chemistry teams work closely with chemical engineers and analytical chemists to deliver the best manufacturing route for new therapeutics. Rahway also houses our preparatory laboratories and the pilot plant to support clinical trials of the therapeutics in our pipeline.

Kenilworth, New JerseyOur Kenilworth, NJ site is currently our corporate headquarters. In addition to a corporate presence, this site also serves as a discovery site where the chemistry team includes Discovery Chemistry, Chemical Biology, High Throughput Experimentation, Modalities, and Discovery Process Chemistry.

Rahway and Kenilworth are both located in northeastern New Jersey with car and train access to New York City. Both sites are surrounded by numerous desirable suburban towns on the train line for easy access to the city. Further south and west, you will find beautiful rural New Jersey towns and the exciting Jersey Shore, all within driving distance to the sites.

Boston, MassachusettsOur Boston, MA site is a state-of-the-art, fully integrated discovery research facility with key therapeutic focus on oncology, immunology, and neuroscience. Our chemistry team includes Discovery Chemistry and Discovery Process Chemistry. Seated in the heart of the Longwood Medical area, our site is surrounded by the world’s leading universities, hospitals, and biotech companies to build on a culture of collaboration both internally and externally.

Cambridge, MassachusettsThe Exploratory Science Center is in the biotech hub of Kendall Square. The site is both disease and modality agnostic; our location enables exploration of a broad spectrum of disease biology using cutting-edge technologies and fit-for-purpose modalities, ranging from small molecules to peptides and bioconjugates to address emerging biology and technology from academic and biotech companies. The chemistry team focuses on early technologies with an emphasis on medicinal chemistry, chemical biology, and bioconjugation.

While being close to Boston’s downtown allows easy access to the cultural and social offerings of the city, the sites are also close to a number of transportation hubs, which allow easy access to the surrounding suburbs and beyond, offering a range of living arrangements from urban to rural.

West Point, PennsylvaniaOur West Point, PA site has a rich history as a hub of small molecule discovery as well as biologics and vaccines research and manufacturing. The chemistry team at West Point includes Discovery Chemistry, Chemical Biology, and Discovery Process Chemistry. Chemists are co-located with scientists in biology, pharmacology, and preclinical development. Key therapeutic areas of focus are neuroscience and infectious diseases.

Located in southeastern Pennsylvania, West Point is accessible by train or car from Philadelphia’s energetic Center City as well as its suburbs. For those who prefer a quieter setting, the hills of rural Pennsylvania can also be found within driving distance of the site.

San Francisco, CaliforniaSouth San Francisco, CA houses one of our newest discovery research facilities, which includes a full complement of Discovery Biology, Biologics, and Discovery Chemistry researchers focusing on treating cardiovascular, renal, metabolic, and ocular diseases. The chemistry team is made up of medicinal chemists, bioconjugation specialists, and Discovery Process chemists.

Nestled in the birthplace of biotechnology on Oyster Point, South San Francisco is accessible via train, shuttle, ferry, or car. As a result of the Bay Area location, one can live in the heart of San Francisco, in a relaxed oceanside town, or across the bay, while still enjoying all the Bay has to offer.

London, United KingdomThe UK Discovery Centre is located at the heart of London’s Knowledge Quarter, a vibrant and rapidly growing life sciences community providing opportunities to collaborate with the European life sciences ecosystem. Our multidisciplinary team of scientists study how changes in fundamental mechanisms of cell homeostasis and resilience during the aging process can lead to diseases that include neurodegeneration. Our discovery scientists are based at interim lab facilities at the London Bioscience Innovation Centre and at the Francis Crick Institute until the Discovery Centre building is complete.

Invent with us! We look forward to hearing from you.

To find out more about career opportunities at Merck, visit our job listing site at jobs.merck.com.

For more than a century, Merck has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases.

Today, Merck continues to be at the forefront of research to deliver innovative health solutions and advance the prevention and treatment of diseases that threaten people around the world.

Copyright © 2021 Merck & Co., Inc., Kenilworth, NJ, USA. All rights reserved.