Some Items of Interest to Process R&D Chemists and Engineers

Happy #OPRD Items of Interest Day!

Another wholesome set of fantastic chemistry highlights and I’m not just saying that because we’ve made this issue…
(Ok maybe a bit) #ChemSky

Call For Papers: Communications & Technical Notes in OPR&D | ACS Publications Chemistry Blog Have a short story to share, or a new protocol that doesn’t fit into a standard full Article? OPR&D is putting out this open Call for Short Papers, welcoming submissions as Communications or Technical...

🚨 Call for Short Papers – Communications & Technical Notes

Have a breakthrough that doesn’t fit a full-length article? #OPRD is now accepting Communications and Technical Notes—short, focused papers designed to move ideas forward faster.

👉 axial.acs.org/organic-chem...

Kilo-Scale-Enabled Route toward PF-07907063, a Type II Brain Penetrant cMET Inhibitor New synthetic methodologies that access complex saturated building blocks enable the synthesis of drug molecules with unique properties. Here, we report collaborative efforts between Pfizer’s Medicina...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 5/n:

From Pfizer Boulder-this #OPRD has it all-enablement, sp2/sp3 hets, cross electrophile couplings, SnAr and more - nice work from @ronhinklin.bsky.social and all
#ChemSky #ChemChat

Cu-Catalyzed C–N Couplings with Benzilamide Ligands A linker fragment used in the preparation of an oncology candidate is efficiently synthesized via Cu-catalyzed C–N coupling. The original route required a Cu-catalyzed coupling, followed by an oxidati...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 4a/n:

The Copper Crew from our Process chem department teamed up again for another #OPRD paper on Cu-catalyzed coupling this time enabling 2° amines with very mild conditions
#ChemSky #ChemChat

Cu-Catalyzed Coupling of Aryl Halides Utilizing Ammonia and Hydroxypicolinamide Ligands The hydroxypicolinamide family of ligands has previously demonstrated utility in Cu-catalyzed C–N couplings and hydroxylation of heteroaryl halides. The application of these ligands has been extended ...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 4/n:

From our Process chem colleagues comes this wonderful #OPRD paper on Cu-catalyzed ammonia/small amine couplings - tons of het scope, easy set up (even worked for me!)
#ChemSky #ChemChat

Building Efficient Diastereo- and Enantioselective Synthetic Routes to trans-Cyclopropyl Esters for Rapid Lead Scale-Up Cyclopropanes play an important role in drug discovery, and synthetic access to variedly substituted systems is an ongoing challenge for chemistry teams. A variety of scalable synthetic routes were de...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 3/n:

MedChem and Process working together to enable chiral cyclopropanes for pre-clinical scaleup - route scouting and development with great teamwork #OPRD #ChemSky #ChemChat

ACS Publications Industry Webinar: Behind the Failures of Suzuki–Miyaura Coupling Scale-Up: A Real-World Case Study

Sign up for our ACS Publications Industry Webinar where we will have #OPRD author Yuhei Yamamoto describe a real-world case study on scale-up of Suzuki-Miyaura couplings.

December 11, 2025 at 9 AM Japan Standard Time (December 10, 2025 at 7 PM ET / 4 PM PT)

access.acspubs.org/SuzukiMiyaur...

Some Items of Interest to Process R&D Chemists and Engineers

Happy #OPRD Items of Interest Day!
#ChemSky #ChemChat

Nominate Articles for the #OPRD 2026 Outstanding Paper of the Year Award by Dec 31!

The award winner will receive:
- $2000 USD prize
- Complimentary travel and registration to ACS Fall 2026 in Chicago to deliver the award lecture
- Award plaque

americanchemical.co1.qualtrics.com/jfe/form/SV_...

Lessons Learned in Organic Process Chemistry

"Failure is the mother of success" -- Read case studies highlighting the knowledge gained from failures and unexpected results in this Lessons Learned in Organic Process Chemistry Special Issue in #OPRD @pubs.acs.org

pubs.acs.org/page/oprdfk/...

Some Items of Interest to Process R&D Chemists and Engineers You have not visited any articles yet, Please visit some articles to see contents here.

This month's #OPRD Items of Interest is out!

pubs.acs.org/doi/10.1021/...

I read #OPRD every day and have found some of the best, most useful synthetic chemistry on its pages
If you need to see how useless IF is then look at these scores

OPRD IF = 3.5
CiteScore = 5.4

(I realize that it’s mainly papers from my industry - it’s still a poor metric for an awesome journal)

Cu-Catalyzed Coupling of Aryl Halides Utilizing Ammonia and Hydroxypicolinamide Ligands The hydroxypicolinamide family of ligands has previously demonstrated utility in Cu-catalyzed C–N couplings and hydroxylation of heteroaryl halides. The application of these ligands has been extended ...

Looking to couple small amines? Even NH3? Super #OPRD from some of my #PfizerChemistry friends with picolinamide ligands for Cu couplings at low %, hi yields/scope-all those hets! So easy I used it to make [REDACTED] inhibitors
This is who I go to for advice – top chemists and friends
#ChemPubs

A very big congrats to the #OPRD winners of the Outstanding Publication of the Year Award, co-sponsored by the ACS Division of Organic Chemistry: Dr. Hsiao-Wu Hsieh and colleagues!
axial.acs.org/organic-chem...

Check out our latest joint Special Issue between #JOrgChem and #OPRD: Excellence in Industrial Organic Synthesis! This is the third edition of this special issue highlighting the industrially relevant work in organic synthesis today.

pubs.acs.org/page/vsi/exc...

wondering why i havent seen #OPRD posts in a while and realised that #OPRD isn't on #ChemSky (I think they are still on the OTHER place)

Kilo-Scale-Enabled Route toward PF-07907063, a Type II Brain Penetrant cMET Inhibitor New synthetic methodologies that access complex saturated building blocks enable the synthesis of drug molecules with unique properties. Here, we report collaborative efforts between Pfizer’s Medicinal Chemistry, Medicinal Chemistry Synthesis Development, and Pharmaceutical Sciences Small Molecule (PSSM) groups for the development of kilogram-scale-enabled synthesis of a type II brain penetrant cMET inhibitor, PF-07907063. The chemistry presented herein demonstrates the importance of implementing a green chemistry approach for developing and applying new transformations throughout the drug development pipeline. Specifically, synthetic planning rooted in the 12 Principles of Green Chemistry led to advancements in deoxygenative photoredox-nickel dual catalysis and cross-electrophile nickel catalysis. The final route significantly lowered the process mass intensity (PMI), increased the yield of the final API, and allowed for the purification of key intermediates through crystallization versus purging impurities via column chromatography, among other improvements.

Another #OPRD asap to highlight is this one from #PfizerChemistry showing a kilo scale route to complex API with all kinds of cool - small hets (pyrazoles!) cyBu, Weix cross electrophile coupling, key synthesis improvements driven by reaction safety…so much to discover in this one #ChemSky

Shackles Off: A Kilo Scale Synthesis of Rawal’s Diene Compared to Danishefsky’s diene, Rawal’s diene suffers from low commercial availability, limited scalability, and obscure stability issues, which strictly limits its usability. Herein, we present an optimized, scalable synthetic protocol that achieves yields suitable for the diene’s semi-industrial production, with adjustments to reagent concentrations, reaction conditions, and isolation procedures to enhance efficiency. Complementing synthetic advancements, this work explores the diene’s physicochemical stability under diverse storage conditions. Rigorous quality control methodologies exploiting nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy facilitate precise monitoring of purity and degradation pathways, establishing robust analytical standards. Additionally, the work demonstrates the utility and advantages of Rawal’s diene in multigram syntheses of 2-alkyl-2,3-dihydro-4H-pyran-4-ones, showcasing its applicability for medicinal chemistry purposes. The findings disclosed in the paper establish a foundation for the broader adoption and commercialization of Rawal’s diene, enabling its integration into academic and industrial workflows.

Also in #OPRD asap is this fantastic manuscript from our friends at Enamine 🇺🇦 outlining improvements allowing a scalable synthesis for Rawal’s diene - some very cool chemistry in here - well done Serhiy, Dima and the crew at Enamine #ChemSky

Some Items of Interest to Process R&D Chemists and Engineers

The April 2025 edition of #OPRD Items of Interest is online chock full of useful synthesis highlights for #ChemSky - too many to list off here (but you might find a couple from #PfizerChemistry)
Definitely worth a look at the cool chem in this issue

Thermally Hazardous 1,3-Dioxolane Coupling Reaction Required for a Pharmaceutical Candidate Starting Material, Made Safer by Employing Process Safety Data as Key Design of Experiments Output Variables The optimization of a ruthenium-catalyzed catechol, terminal-alkyne coupling reaction to form a key benzodioxolane intermediate toward Lotiglipron is described. This transformation required the use of...

Wonderful #OPRD from #PfizerChemistry (UK) with Snapdragon prepping a key intermediate using process safety endpoints as part of DOE studies #MyOtherCompoundIsAKetal

Preclinical Toxicology Supply for a Complex API Enabled by Asymmetric Catalysis and Rapid Chemical Development: IL-17A Inhibitor LY3509754 The chemical development and production of sufficient amounts of IL-17A inhibitor LY3509754 to enable preclinical toxicology studies is described. LY3509754 is a complex small molecule that features t...

#ChemSky Super #OPRD out today from #LillyChem on an IL17 compound from discovery to process chem. A ln extensive look at all the chemistry needed to bring this complex API to key preclinical studies
A great read!

Building Efficient Diastereo- and Enantioselective Synthetic Routes to trans-Cyclopropyl Esters for Rapid Lead Scale-Up Cyclopropanes play an important role in drug discovery, and synthetic access to variedly substituted systems is an ongoing challenge for chemistry teams. A variety of scalable synthetic routes were de...

Chiral cyclopropanes?
We got em - check out this new #OPRD from my #PfizerChemistry colleages from MedChem, HTE, Biocatalysis and Process coming together to enable a wonderful method to key fragments. Neat story on how it all came together (chiral Corey-Chaykovsky alert!)

Comprehensive Synthetic Route Redesign of AZD5991: A High-Complexity Atropisomeric Macrocycle We describe our approach to the total synthesis of AZD5991 (1) from a process development perspective through the complete redesign of our synthetic strategy from the ground up. The size and complexity of small-molecule therapeutic targets have continued to increase over recent decades. One such example, 1, is arguably the most complex active pharmaceutical ingredient (API) in AstraZeneca’s small molecule development portfolio to date and poses formidable synthetic challenges. The previous racemic synthesis of 1 was sufficient to supply early clinical activities; however, the route was not deemed commercially viable and had significant environmental challenges. The identification of a long-term sustainable route was therefore critical to enable the robust manufacture of drug substance for later clinical activities and launch. We report exploration of asymmetric approaches toward the atropisomeric core, new routes toward each of the four heterocyclic building blocks, including a divergent pyrazole functionalization, and final assembly in a scalable and controlled macrocyclization process. These improvements resulted in a 49% reduction in step count and 95% reduction in projected waste generation.

For #ChemSky #SynthesisSaturday here’s a very cool #OPRD on a process scalemacrocycle from GSK and my pal Ollie Ring
I’ve seen this story in talk form and there’s some excellent chemistry in here

Check out both of the Items of Interest Highlights articles in this month's #OPRD issue:
pubs.acs.org/doi/10.1021/...
pubs.acs.org/doi/10.1021/...

Special Issue Alert! Analytical control strategies play a major role in quality assurance and reaction monitoring in modern process chemistry.

Analytical Control Strategies for Process Chemists in #OPRD

Special Issue: pubs.acs.org/page/oprdfk/...

Editorial: pubs.acs.org/doi/10.1021/...

#ChemSky

Stereoselective Synthesis of Mirogabalin via 1,4-Selective Addition of Lithioacetonitrile to Alkylidene Malonate The synthesis of mirogabalin was studied for industrial production and an alternative to Daiichi–Sankyo’s method was established. The developed synthesis involves the introduction of a two-carbon unit with the stereoselective 1,4-selective addition of lithioacetonitrile to alkylidene malonate and one-carbon degradation by the Hofmann rearrangement. The precursor for the Hofmann rearrangement was readily prepared from the 1,4-adduct via a one-pot reaction involving decarboxylation, hydrolysis, and hydration.

KANEKA introduces a stereoselective synthesis of mirogabalin featuring a novel stereo- and 1,4-selective addition of lithioacetonitrile to alkylidene malonate #OPRD #chemsky

pubs.acs.org/doi/10.1021/...

Methodologies for the Formation of 2-Substituted Oxetanes: Synthesis of (S)-Oxetan-2-ylmethyl Tosylate The compound (S)-oxetan-2-ylmethyl tosylate 1 was identified as a key synthetic fragment for the introduction of the 2-substituted oxetane functionality in potential drug candidates under development ...

This is a very cool #OPRD showing some excellent enablement of a small piece of a drug candidate from my former #PfizerChemistry colleagues in Sandwich UK.

See also: “Oh cute Medchem route…here’s 6 papers with better chemistry”

[Narrator: it was the Medchem route from Scott’s lab]

Commercial Route Development of Sigma-2 Receptor Modulator, CT1812 Leveraging Photoflow, and HTS Technologies A second-generation synthesis of CT1812, a sigma-2 receptor modulator (ligand), was developed from readily available starting materials to support late-stage clinical needs. An AIBN-induced thermal be...

The development story behind the second generation synthesis of Cognition Therapeutics' sigma-2 receptor modulator, zervimesine (CT1812) can be found here:
pubs.acs.org/doi/10.1021/...
#chemsky #OPRD

Some Items of Interest to Process R&D Chemists and Engineers

Happy #OPRD Items of Interest Day!! Your monthly guide for cool synthesis lit highlights
This month with Industry contributions from #Merck #AbbVie #GSK & #Pfizer and cool work from @sarponggroup.bsky.social @reiswoman.bsky.social Sharma (U Leuven) and so many more

Synergizing Process Conditions, Water Sensitivity, and Kinetic Mechanisms to Optimize Sodium Salicylate Yield in Sodium Phenol Carboxylation Sodium salicylate can be formed by carboxylation of solid sodium phenol particles with carbon dioxide gas under certain conditions. Single-factor experiments were carried out with self-made dried sodium phenol particles in a batch high-pressure reactor. It was determined that the carboxylation reaction of sodium phenol particles was more suitable under the conditions of a reaction temperature of 160 °C, a reaction pressure of 0.55 MPa, a reaction time of about 40 min, and a stirring speed of 50 rpm. Besides that, the water content of the material also had important effects on the yield. Through the establishment of the kinetic model of the carboxylation reaction between solid sodium phenol particles and carbon dioxide gas, the control step of the reaction temperature at 150 and 160 °C was determined as ash layer diffusion, and the kinetic equation was further calculated. The research results can provide the basic technological conditions and kinetic data of the carboxylation reaction of sodium phenol particles and provide a reference for the development of a continuous and efficient production process of sodium phenol carboxylation.

Industrial production of chemicals is such a different beast to lab chemistry

I would have never considered direct carboxylation of phenol to make salicylic acid…
#OPRD #ChemSky