Scott Bagley

@bagphos.bsky.social

3 months ago

Annulative Skeletal Diversification of Pyrimidines to Expanded Heteroaromatic Space Single-atom skeletal editing has recently emerged as a powerful strategy for the direct diversification of the heterocyclic cores of various compounds. Yet, methods that enable monocycle-to-bicycle tr...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 12b:

I’m so excited how this one turned out with the @sarponggroup.bsky.social led by Philip Speiß. A one-pot fusion of 2 heterocycles - a whole new way in to key 6/5 and 6/6 pharmacophores @jacs.acspublications.org

#ChemSky #ChemChat

Scott Bagley

@bagphos.bsky.social

3 months ago

Oxygen migration into carbon–carbon single bonds by photochemical oxidation - Nature Synthesis Heteroatom insertions into chemically inert carbon–carbon single bonds are rare compared to their unsaturated analogues. Now, ligand-to-metal charge transfer offers a promising entry point for oxygen ...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers
12a:

What a pleasure it was to work with the @uwyoongroup.bsky.social and @tehshik.bsky.social on this sp3 skeletal rearrangement paper - wonderful job by Caitlin, Cade and all - I’m still floored by this rxn #ChemSky #ChemChat

Scott Bagley

@bagphos.bsky.social

3 months ago

Development of a Scalable Synthesis of a HPK1 Inhibitor Featuring a Direct α-Arylation of Boc-Protected N,N-Dimethylamine by Palladium-Mediated Negishi Cross-Coupling The development of an improved synthesis of the potent HPK1 inhibitor, compound 1, is described. Two primary strategies were explored during this process: metallaphotoredox decarboxylative coupling an...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 11/n:
A super cross line/site collaboration among Groton and La Jolla medchem teams with our Process chemists comes this fantastic het synthesis w/ innovative BOCNMe2 zincate coupling #JOC #ChemSky #ChemChat

Scott Bagley

@bagphos.bsky.social

3 months ago

Sulfur fluoride exchange with carbon pronucleophiles Aryl alkyl sulfones are an important class of compounds in drug discovery; thus, new methods toward their synthesis are desirable. A general sulfur fluoride exchange (SuFEx) method to couple aryl sulf...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 10/n:

Alkylation of R-SO2F with carbon nucleophiles out in @chemicalscience.rsc.org
- a collaboration with the awesome @ballnchemist.bsky.social
and his amazing undergrads at @pomonacollege.bsky.social
#ChemSky #Chemchat

Scott Bagley

@bagphos.bsky.social

3 months ago

Accelerating Medicinal Chemistry: A C(sp3)‐Rich Fragment Toolbox for Redox‐Neutral Cross‐Coupling It is introduced in this report a unified toolbox comprising of 15 sulfonyl hydrazide reagents that enable the redox-neutral radical cross-coupling of 14 distinct C(sp3)-rich small fragments onto (he...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 9/n:

An industry collab with our Pfizer La Jolla colleagues (w/BMS+BioGen) and @BaranLabReads comes this wonderful medchem look at sulfonyl hydrazides as powerful sp2-sp3 coupling agents #ChemSky #ChemChat

Scott Bagley

@bagphos.bsky.social

3 months ago

A bifunctional boronic acid/phosphorus(V) organocatalyst for the direct room-temperature amidation of carboxylic acids An organocatalyst containing boronic acid and phosphine oxide groups enables the coupling of carboxylic acids and amines at room temperature to achieve a sustainable route to the amide bonds present i...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 8/n:

Room temp catalytic amide formation with this ingenious bifunctional B-P reagent from our process chem in collab with the Sandford Lab @ UTSA
#ChemSky #ChemChat

Scott Bagley

@bagphos.bsky.social

3 months ago

C(sp2)–C(sp3) Suzuki–Miyaura Cross-Coupling Using gem-Bis(boronates) A strategy utilizing gem-bis(boronates) as a stable and easily accessible surrogate for the analogous monoboronate and their efficient use in Suzuki–Miyaura cross-couplings to access the highly intere...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 7/n:

From my colleague Jun Xiao and our MedChem teams in collab with our WuXi partners this is a facile sp2-sp3 Suzuki with tons of het scope using alkyl gem-(bis)boronates
#ChemSky #ChemChat

Scott Bagley

@bagphos.bsky.social

3 months ago

Desulfinative Cross-Coupling as a Method to Overcome Problematic Suzuki–Miyaura Reactions of Pharmaceutically Relevant Heteroaromatic Boronates The well documented difficulties associated with direct (hetero)arylation of aza-aromatics (e.g., azines) at the α-position to nitrogen led to a collaborative project between the Willis group at Oxfor...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 6/n:

This wonderful review of desulfinative coupling in med chem as an alternative to traditional Suzuki - esp effective for heterocycles - collab with the Willis lab @rhpdcu.bsky.social
Uses in PMC to scale up
#ChemSky #ChemChat

Scott Bagley

@bagphos.bsky.social

3 months ago

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

Scott Bagley

@bagphos.bsky.social

3 months ago

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

Scott Bagley

@bagphos.bsky.social

3 months ago

Alkyl sulfonyl fluorides as ambiphiles in the stereoselective palladium(II)-catalysed cyclopropanation of unactivated alkenes - Nature Synthesis The ambiphilic reactivity of alkyl sulfonyl fluorides in stereoselective cyclopropanation under Pd(II) catalysis is reported. The method provides convenient access to cis-disubstituted cyclopropanes t...

Interrupting #12DaysOfPapers to share this beauty from #PfizerChemistry, @mykhailiukchem.bsky.social Enamine, @pengliugroup.bsky.social and a host of Scripps La Jolla folks now out in @natsynth.nature.com - stereocontrolled cyclopropanes from Alkyl-SO2F & olefins with a Pd (II-IV) catalytic cycle

Scott Bagley

@bagphos.bsky.social

3 months ago

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

Scott Bagley

@bagphos.bsky.social

3 months ago

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

Scott Bagley

@bagphos.bsky.social

3 months ago

Palladium-Catalyzed Enantioselective Stereodivergent Desymmetrization of Cyclic 1,4-Allyldiboronates In the presence of a chiral palladium-based catalyst, 1,4-diboryl-2-alkenes undergo enantioselective cross-coupling that results in desymmetrization of the substrate structure. Depending on the reaction conditions and the choice of ligand, the reaction can occur with cis or trans selectivity, allowing the construction of an array of different substituted chiral carbocycles in an enantiomerically enriched fashion.

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 2/n:
From my process chem colleagues in collaboration with the Morken lab (Boston College) - a desymmetrization of 1,4 cyclic bisboronates @jacs.acspublications.org
#ChemSky #ChemChat

Scott Bagley

@bagphos.bsky.social

3 months ago

Microwave-Assisted Synthesis of Heterocycles via Rhodium(III)-Catalyzed C–H Activation: Norbornadiene as an Acetylene Equivalent General procedures for the rhodium-catalyzed annulation of aryl/heteroaryl O-pivaloyl hydroxamic acids and norbornadiene have been developed. Employing norbornadiene as an acetylene equivalent enables...

My favorite 2025 #PfizerChemistry publications #12daysOfPapers 1/n: From my La Jolla colleagues this is a cool use of Rh-catalyzed C-H activation followed by retro Diels-Alder to provide useful med chem heterocycles #OrgLett
#ChemSky #ChemChat

Scott Bagley

@bagphos.bsky.social

3 months ago

two men are sitting at a table in a kitchen talking to each other . one of the men is wearing a beanie . ALT: two men are sitting at a table in a kitchen talking to each other . one of the men is wearing a beanie .

As 2025 comes to a close I'm taking a look back at some fantastic 2025 #PfizerChemistry publications and wanted to share a few of my favorites so watch here for the next few days #12daysOfPapers

Scott Bagley

@bagphos.bsky.social

1 year ago

Sustainable Solvents in Metallaphotoredox Catalysis Metallaphotoredox chemistry has emerged as a powerful tool to access synthetically challenging motifs in a rapid and efficient manner. Generally, photoredox catalysis is recognized as a green technology, avoiding highly reactive chemicals and using ambient temperatures. Nevertheless, solvent choice is often overlooked with commonly used hazardous sulfoxides, ethers, and amides such as DMF or DMAc. Herein, we emphasize the importance of sustainable solvents in photoredox chemistry and their application to process chemistry. We present alternative conditions for two of the most utilized photocatalytic reactions in the pharmaceutical industry.

11/ #12DaysofPapers #ChemSky
Presenting some of my favorite #PfizerChemistry papers from 2024
This one is an internal collab between Discovery and Process chem exploring the application of greener solvents in photoredox chemistry - good results with acetone and IPAc

Scott Bagley

@bagphos.bsky.social

1 year ago

Carbon quaternization of redox active esters and olefins by decarboxylative coupling The synthesis of quaternary carbons often requires numerous steps and complex conditions or harsh reagents that act on heavily engineered substrates. This is largely a consequence of conventional pola...

10/ #12DaysofPapers #ChemSky
Presenting some of my favorite #PfizerChemistry papers from 2024
Next up is a multi-center #ChemCollabs from our Groton and La Jolla labs with @shenvi.bsky.social, the Baran lab and #Biogen out in @science.org forming tertiary sp3 centers from RAEs or olefins

Scott Bagley

@bagphos.bsky.social

1 year ago

Anti-selective Cyclopropanation of Nonconjugated Alkenes with Diverse Pronucleophiles via Directed Nucleopalladation A facile approach to obtaining densely functionalized cyclopropanes is described. The reaction proceeds under mild conditions via the directed nucleopalladation of nonconjugated alkenes with readily a...

9/ #12DaysofPapers #ChemSky
Presenting some of my favorite #PfizerChemistry papers from 2024
From #JACS a collab between the Engle lab at Scripps and our La Jolla chemistry group delivered fantastic work to chiral cyclopropanes-wide tolerability and selectivity

Scott Bagley

@bagphos.bsky.social

1 year ago

Copper-Catalyzed Hydroxylation of Aryl Halides Using Hydroxypicolinamide Ligands Hydroxylation of haloarenes is a fundamental transformation in synthetic organic chemistry. Hydroxypicolinamide ligands enable the efficient Cu-catalyzed hydroxylation of heteroaryl halides with a wide functional group tolerance. The Cu-MPBS system, originally designed for C–N coupling, enables the Cu-catalyzed hydroxylation of aryl bromides. A related derivative, Cu-HMPS, provides exceptional reactivity and purity for hydroxylation of aryl bromides, aryl iodides, and activated aryl chlorides. Ortho-activated substrates have shown exceptionally high reactivity and selectivity for Cu-catalyzed hydroxylation. More difficult aryl chlorides, substrates that require a higher activation temperature (120 °C), may be hydroxylated by the Cu-DMPS system that has superior intrinsic ligand stability. Reaction conditions may be tuned to target substrates through ligand, solvent, and base selection. Safe and robust processing conditions have been designed utilizing aqueous KOH, K2CO3, or K3PO4 in sulfolane or sulfolane and alcohol blends.

8/ #12DaysofPapers #ChemSky
Presenting some of my favorite #PfizerChemistry papers from 2024
Another in #OPRD from my Process chem colleagues with a Cu-catalyzed hydroxylation of (Het)Ar-X
Personal note: these folks are my go-to problem solvers, couldn’t ask for better friends and scientists

Scott Bagley

@bagphos.bsky.social

1 year ago

Commercial Route Development Toward PF-07265807, an AXL-MER Inhibitor Oncology Candidate Our route scouting efforts toward finding the most efficient construction of PF-07265807 (ARRY-067) in readiness for process development prior to commercial manufacture are described. ARRY-067 contains the azaindazole (1H-pyrazolo [3,4-b]pyridine) building block that is common to many pharmaceuticals and bioactive agents. Herein, our novel approach to this challenging structural motif is described where an oxazoline ring-opening cyclization cascade triggered by the addition of hydrazine reveals the target 3-alaninol-substituted azaindazole in one step. An improved synthesis of the uracil carboxylic acid coupling partner is also described. Overall, the new route is six steps shorter than the enabling route, minimizes protecting group manipulations, and avoids the use of transition metal catalysis.

6/ #12DaysofPapers #ChemSky. From #OPRD here is more fantastic work from our #PfizerChemistry process towards an oncology candidate - I really enjoy all of the wonderful ring building in this paper - and Meldrum’s acid makes everything better

Scott Bagley

@bagphos.bsky.social

1 year ago

Transition-Metal-Free Synthesis of a Densely Functionalized Benzodioxole Intermediate toward Lotiglipron A decagram-scale preparation of the key intermediate (±)-2-(4-bromo-2-methylbenzo[d][1,3]dioxol-2-yl)-5-chloropyridine is described. Key steps involve a double nucleophilic substitution of 3-bromocate...

5/ #12DaysofPapers #ChemSky. From #OPRD here is some fantastic work from our #PfizerChemistry process folks towards an important ketal fragment of Lotiglipron using some effective ring building methodology

Scott Bagley

@bagphos.bsky.social

1 year ago

Computational Methods Enable the Prediction of Improved Catalysts for Nickel-Catalyzed Cross-Electrophile Coupling Cross-electrophile coupling has emerged as an attractive and efficient method for the synthesis of C(sp2)–C(sp3) bonds. These reactions are most often catalyzed by nickel complexes of nitrogenous liga...

4a/ #12DaysofPapers #ChemSky. This 2024 favorite is a #PfizerChemistry collab with the Weix (Wisconsin) and Sigman (Utah) labs towards computationally designed ligands for Ni-catalyzed cross electrophile coupling. Improvements in selectivity up to 300% #ChemCollabs

Scott Bagley

@bagphos.bsky.social

1 year ago

Nitro-sulfinate Reductive Coupling to Access (Hetero)aryl Sulfonamides A method to assemble (hetero)aryl sulfonamides via the reductive coupling of aryl sulfinates and nitroarenes is reported. Various reducing conditions with sodium bisulfite and with or without tin(II) ...

3/n #12DaysofPapers #ChemSky. Here’s another fav 2024 sulfur(VI) paper from #PfizerChemistry and the Ley lab at Cambridge making sulfonamides (my fav functional group) in a reductive coupling with sulfinates and hetAr-nitro compounds pubs.acs.org/doi/10.1021/...

Scott Bagley

@bagphos.bsky.social

1 year ago

2/n #12DaysofPapers #ChemSky I’m a big fan of S(VI) and excited to see the #ChemCollabs continue between #PfizerChemistry and the Willis Lab @rhpdcu.bsky.social at Oxford including this facile Cu-catalyzed access to sulfinates using SMOPS - one of the best reagent names pubs.acs.org/doi/10.1021/...

Scott Bagley

@bagphos.bsky.social

1 year ago

A metal-free strategy to construct fluoroalkyl–olefin linkages using fluoroalkanes We present a metal-free strategy to access fluoroalkyl–olefin linkages from fluoroalkane precursors and vinyl-pinacol boronic ester (BPin) reagents. This reaction sequence is templated by the boron re...

1/n - #12DaysofPapers
Highlighting this #PfizerChemistry #ChemCollabs with the Szymczyk Lab @ Michigan Chem enabling C-H coupling of fluoroalkyls with vinyl-BPins to access some really neat complex fragments ready for additional functionalization
pubs.rsc.org/en/content/a...

Scott Bagley

@bagphos.bsky.social

1 year ago

a man wearing a beanie and a black jacket is smiling and holding a piece of food . ALT: a man wearing a beanie and a black jacket is smiling and holding a piece of food .

As 2024 comes to a close I've had a chance to take a look back at some fantastic 2024 #PfizerChemistry publications and wanted to share a few of my favorites so watch here for the next few days #12daysOfPapers #ChemSky