Organic Process Research & Development最新文献

{"title":"Development of the Commercial Manufacturing Process for Xanomeline Tartrate, an Active Pharmaceutical Ingredient in KarXT","authors":"Joseph Ryan,&nbsp;Aida Ajaz,&nbsp;Rajender Vemula,&nbsp;Christopher R. H. Hale,&nbsp;Giorgio Attardo,&nbsp;MVRCH Murthy,&nbsp;Yolanda Gasanz,&nbsp;Vijaya B. Gondi","doi":"10.1021/acs.oprd.6c00185","DOIUrl":"10.1021/acs.oprd.6c00185","url":null,"abstract":"<p>Development of the commercial manufacturingstrategy and processemployed for xanomeline tartrate (<strong>KTX-001)</strong>, a key activepharmaceutical ingredient (API) in KarXT, is described. The developmentprocess involved identifying efficient processes for key bond-formingsteps, including the conversion of regulatory starting material nicotinaldehyde(<strong>1</strong>) to stage 1 regulatory intermediate chlorothiadiazole <strong>2</strong>, nucleophilic aromatic displacement of the chlorine atomwithin <strong>2</strong> with 1-hexanol followed by methylation to generatestage 2 regulatory intermediate pyridinium <strong>4</strong>, and selectivepartial reduction of the pyridine ring to produce the API freebase,which after tartrate salt formation gave access to stage 3 regulatoryintermediate crude xanomeline tartrate (<strong>crude KTX-001</strong>). A recrystallization process was developed to provide the drugsubstance xanomeline tartrate (<strong>KTX-001</strong>) in an overallyield of 35% from nicotinaldehyde (<strong>1</strong>) with HPLC purityof &gt;99.0% on scales of 500+ kilograms per batch, suitable for reliablesupply of this commercial drug substance.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2694–2708"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148476482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Scalable Amidation-Dehydration Telescope Process for the Synthesis of Ibuzatrelvir","authors":"Russell F. Algera,&nbsp;Cindy Duong,&nbsp;Doug Farrand,&nbsp;Michael Herr,&nbsp;Gary R Jolin,&nbsp;Melissa Lee,&nbsp;Lesly Mejia,&nbsp;David W. Place,&nbsp;Rachel Ruest,&nbsp;Courtney Talicska,&nbsp;R. Matthew Weekly,&nbsp;Gerald A. Weisenburger,&nbsp;Kaitlyn Gray,&nbsp;Truong N. Nguyen","doi":"10.1021/acs.oprd.6c00095","DOIUrl":"10.1021/acs.oprd.6c00095","url":null,"abstract":"<p>Ibuzatrelvir is a second-generation, orally administeredinhibitorof the SARS-CoV-2 M^pro that has enhanced metabolic stabilitycompared to nirmatrelvir. Although early manufacturing campaigns enabledrapid large-scale supply, the final amidation–dehydration sequencefaced significant challenges in robustness, impurity control, anddownstream processing. In this report, we detail a streamlined telescopedprocess comprising a robust and efficient 2-chloro-1-methylpyridinium <em>p</em>-toluenesulfonate (CMPT)-mediated amidation followed bya clean trifluoroacetic anhydride (TFAA)-driven dehydration to overcomeexisting limitations. Process refinements in distillation, solventexchange, and crystallization delivered a reproducible, sustainableroute that was demonstrated at multikilogram scale. The optimizedprocess afforded ibuzatrelvir in high yield, purity, and potency whilemarkedly reducing process mass intensity (PMI) and cycle time, establishingan efficient and industrially viable approach for long-term manufacturing.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2616–2624"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148974114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computer-Aided Solvent Selection for the Design of Integrated Synthesis, Crystallization, and Isolation Processes","authors":"Mohamad H. Muhieddine,&nbsp;Suela Jonuzaj,&nbsp;Oliver Watson,&nbsp;Sara Ottoboni,&nbsp;Jan Sefcik,&nbsp;Chris J. Price,&nbsp;Shekhar K. Viswanath,&nbsp;Alan Armstrong,&nbsp;Amparo Galindo,&nbsp;George Jackson,&nbsp;Claire S. Adjiman","doi":"10.1021/acs.oprd.6c00168","DOIUrl":"10.1021/acs.oprd.6c00168","url":null,"abstract":"<p>The extensive useof solvents in pharmaceutical manufacturing hasmajor impacts on overall process performance and final product quality.Solvent selection often requires tedious and resource-intensive experimentalinvestigations. Nevertheless, the growing interest in embedding sustainablepractices in process development workflows has motivated pharmaceuticalmanufacturers and researchers to deploy digital tools for enhancingprocess understanding and guiding the design of greener materialsand processes. In this work, a computer-aided mixture/blend design(CAM^<em>b</em>D) methodology is developed to identifysimultaneously the optimal solvent or solvent/antisolvent mixtures,mixture compositions, and process conditions in end-to-end processes,considering integrated synthesis, crystallization, and isolation.Within the proposed approach, thermodynamic models are used to coupleproperty prediction with process modeling to describe pharmaceuticalprocess systems, while mathematical optimization techniques are appliedto search the large design space of potential solvents and processconditions and identify the most promising designs among thousandsof possible options. Further consideration is also given to the integrateddesign of reaction, crystallization, and wash solvents, where designdecisions across the entire process are interlinked. The methodologyis applied to the synthesis, crystallization, and isolation of mefenamicacid as a case study, while considering a broad range of process-widekey performance indicators (KPIs) that quantify product quality andresource efficiency, such as product purity and process energy consumption.In order to explore the trade-offs between competing KPIs, the proposedapproach is extended to solve multiobjective design problems and generatea list of Pareto-optimal designs. The results highlight that the optimaldesigns are strongly dependent on the criteria considered and motivatethe need for an integrated approach to solvent selection and processdesign. The findings of this study are expected to contribute to thedigitalization of solvent selection for the accelerated developmentof sustainable pharmaceutical processes.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2672–2693"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149050197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"End-to-End Continuous Synthesis and Crystallization of Clopidogrel Bisulfate: Process Intensification and Solid-Form Control","authors":"Feiyan Zhan,&nbsp;Mengran Du,&nbsp;Wenbo Jiang,&nbsp;Yan Chen,&nbsp;Peiwen Liu,&nbsp;Yufang Xu,&nbsp;Xuhong Qian,&nbsp;Huan He,&nbsp;Honglin Li,&nbsp;Weiping Zhu","doi":"10.1021/acs.oprd.6c00273","DOIUrl":"10.1021/acs.oprd.6c00273","url":null,"abstract":"<p>The conventional batch manufacturing of clopidogrel bisulfateisconstrained by low process efficiency and poor control over pharmaceuticallypreferred yet metastable Form I. Herein, we report an end-to-end continuousmanufacturing process that combines multistep synthesis with a nucleation–growthdecoupled crystallization strategy to address both challenges. Throughthe integration of solid-acid-catalyzed esterification, three-feedsulfonylation, phase-transfer catalyst (PTC)-enabled S_N2 reaction, membrane-based phase separation, inline solvent exchange,and continuous crystallization, this integrated platform directlyconverts commercially available starting materials into sphericalForm I crystals with a narrow size distribution (Span = 0.42) withoutisolation of intermediates. The system operated continuously for 7.5h, achieving a 70% overall isolated yield and 97% S-enantiomeric purity.Compared with batch processing, the platform reduces total processingtime by 3.8-fold, halves the <em>E</em>-factor and processmass intensity (PMI), and increases space-time yield (STY) by 20-fold.The integrated process offers a scalable approach for continuous productionof pharmaceutical solids while maintaining control over both the molecularsynthesis and product solid form.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2811–2821"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148933638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety Hazard of the Thermal Decomposition of Difluoromethyl and -Methoxy Arenes Catalyzed by Boron Derivatives","authors":"Christine Fannes,&nbsp;Matthieu Jouffroy","doi":"10.1021/acs.oprd.6c00306","DOIUrl":"https://doi.org/10.1021/acs.oprd.6c00306","url":null,"abstract":"<p>A thermal safety investigation wasconducted followingmultiplelaboratory incidents involving difluoromethoxy-substituted aryl boronicacids. Differential scanning calorimetry (DSC) revealed that compoundsbearing both a difluoromethoxy (or difluoromethyl) group and a boronicacid or boronate ester exhibit pronounced low-temperature exothermicdecomposition. This instability was observed both intramolecularlyand through intermolecular interactions among otherwise thermallystable components. The severity of decomposition was enhanced by thesteric proximity between the two functional groups and could be triggeredby catalytic quantities of boron-containing species or contact withborosilicate glass. Structural modifications, notably the replacementof the boronic acid group, significantly improved thermal stability.These findings identify a previously underappreciated thermal hazardassociated with this functional group combination and have importantimplications for compound design, storage, and process safety evaluation.Finally, an initial mechanistic investigation of the decompositionprocess as well as recommendations for compound handling are presented.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2833–2838"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149188013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Development of Ibuzatrelvir: Navigating Polymorph and Crystallization Challenges in a Protecting Group-Free Direct Amidation and Amidation-Dehydration Sequence","authors":"María González-Esguevillas,&nbsp;Aaron F. Baldwin,&nbsp;Pablo J. Cabrera,&nbsp;Yanfei Guan,&nbsp;Chintelle James,&nbsp;Nahian Khan,&nbsp;Samir A. Kulkarni,&nbsp;Johnny W. Lee,&nbsp;Melissa Lee,&nbsp;Emily Lennert,&nbsp;Yiyang Liu,&nbsp;Jeffrey M. Massicott,&nbsp;Asaad Nematalla,&nbsp;Robert J. Pearson,&nbsp;David W. Place,&nbsp;Giselle P. Reyes,&nbsp;Hud Risley,&nbsp;Philipp C. Roosen,&nbsp;Michael Stanley,&nbsp;Jeanene E. Tickner,&nbsp;Aining Wang,&nbsp;Rebecca B. Watson,&nbsp;Gerald A. Weisenburger,&nbsp;Christophe Allais","doi":"10.1021/acs.oprd.6c00128","DOIUrl":"10.1021/acs.oprd.6c00128","url":null,"abstract":"<p>Ibuzatrelviris an orally bioavailable, next-generation clinicalcandidate developed for the treatment of COVID-19 infections. It wasidentified during the pandemic, prior to the approval of PAXLOVID,and displays a more favorable pharmacokinetic profile than nirmatrelvir.Consequently, the initial development of ibuzatrelvir proceeded underhighly accelerated timelines. This report details the optimizationof the end-stage synthesis sequence and its advancement throughoutthe initial clinical production campaigns. The study highlights anefficient protecting group-free amidation of <em>tert</em>-leucine and describes a complex isolation process following a telescopedamidation-dehydration cascade leading to ibuzatrelvir with a 30% increasein yield. The finalized synthetic route was successfully scaled up,enabling the manufacture of several hundred kilograms to support clinicalresearch initiatives.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2637–2648"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148974115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impurity That Was Not: A Persistent Efinaconazole Signal Revealed as an Isotopologue","authors":"Matteo Baudino,&nbsp;Alessandro Barozza,&nbsp;Piergiorgio Bettoni,&nbsp;Martino Veronese,&nbsp;Stefano Ferrandi,&nbsp;Jacopo Roletto","doi":"10.1021/acs.oprd.6c00258","DOIUrl":"10.1021/acs.oprd.6c00258","url":null,"abstract":"<p>Identificationof process-related impurities is a routine taskin the optimization and manufacturing of APIs. The identificationof these contaminants enables researchers to develop appropriate strategiesto purge them or prevent their formation. In many cases, impurityidentification is straightforward, relying on an understanding ofthe synthetic process and the reactivity of the reagents, which allowsresearchers to hypothesize the formation of specific byproducts thatare often indeed generated during synthesis. In other instances, however,certain impurities are extremely difficult to characterize, and theiridentification becomes a challenging and demanding task, particularlywhen present at very low levels. This article describes the time-and resource-intensive effort required to identify and characterizea nonpurging impurity in efinaconazole that elutes in close proximityto the API peak and is consistently detected at 0.06% (a/a), posinga potential Out of Specification risk during industrial production.The impurity was ultimately identified as an isotopologue of efinaconazoleexhibiting subtly distinct physicochemical properties, an uncommonbehavior for isotopologue species.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2803–2810"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Stereoselective Route for Kilogram-Scale Synthesis of STING Agonist BMS-986301","authors":"Miao Yu,&nbsp;Bin Zheng,&nbsp;Chao Hang,&nbsp;Geoffrey E. Purdum,&nbsp;Daniel S. Treitler,&nbsp;Melda Sezen-Edmonds,&nbsp;Changxia Yuan,&nbsp;Adam J. Freitag,&nbsp;Siwei Guo,&nbsp;Guanghui Zhu,&nbsp;Jason Zhu,&nbsp;Carlos Alberto Pons Sierpermann,&nbsp;Benjamin Hritzko,&nbsp;Jonathan G. Shackman,&nbsp;Sloan Ayers,&nbsp;Hua Chia Tai,&nbsp;Weiqing Fu,&nbsp;Brian L. He,&nbsp;Jim Paulson,&nbsp;Qinggang Wang,&nbsp;Amanda J. Rogers,&nbsp;Michael A. Schmidt,&nbsp;Benjamin Cohen","doi":"10.1021/acs.oprd.6c00219","DOIUrl":"10.1021/acs.oprd.6c00219","url":null,"abstract":"<p>Following the discovery of a chiral P(V) reagent to enablediastereoselectivesynthesis of stereogenic thiophosphoramidates, we have developed ascalable synthesis to deliver kilogram quantities of the STING agonistBMS-986301. The route not only reduced the number of steps comparedto the enabling route but also avoided the use of hazardous reagents.Further development enabled the use of crystallizations to isolateintermediates, effectively eliminating six chromatographic purifications.This resulted in an eightfold improvement in yield and 90% reductionin process mass intensity (PMI). The route was successfully implementedin a pilot-plant campaign to deliver 1.65 kg of BMS-986301 (<strong>1</strong>) and was therefore deemed suitable as a long-term optionfor commercial synthesis.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2767–2782"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical Synthesis of Methyl N2-(tert-butoxycarbonyl)-N4-(1-(tert-butyl)-1H-pyrazol-4-yl)-L-asparaginyl-L-phenylalaninate Utilizing Continuous-Flow Technology","authors":"Xueyi Zhang,&nbsp;Praveen Kumar Gajula,&nbsp;Maksim Vasilev,&nbsp;Graham Hibbert,&nbsp;Anji Chen,&nbsp;Gopal Sirasani,&nbsp;Aravind S. Gangu,&nbsp;Bo Qu,&nbsp;Chris H. Senanayake","doi":"10.1021/acs.oprd.6c00305","DOIUrl":"10.1021/acs.oprd.6c00305","url":null,"abstract":"<p>A practical synthesis of methyl <em>N</em>²-(<em>tert</em>-butoxycarbonyl)-<em>N</em>⁴-(1-(<em>tert</em>-butyl)-1<em>H</em>-pyrazol-4-yl)-<em>L</em>-asparaginyl-<em>L</em>-phenylalaninate(<strong>5</strong>)utilizing two continuous-flow processes is reported. The first isthe trickle-bed continuous-flow hydrogenation of the nitro compound1-<em>tert</em>-butyl-4-nitro-1H-pyrazole (<strong>1</strong>)on a multikilogram scale, followed by T₃P-mediated amidecoupling in flow with the dipeptide (<em>S</em>)-3-((tert-butoxycarbonyl)amino)-4-(((<em>S</em>)-1-methoxy-1-oxo-3-phenylpropan-2-yl)amino)-4-oxobutanoicacid (<strong>4</strong>) to obtain compound <strong>5</strong> in an overall80–84% yield and &gt;99.9 A% HPLC purity. <em>In situ</em> ReactIR was applied for real-time reaction monitoring. A catalyst-bedpacking protocol was engineered to mitigate pressure drop and maintaincatalyst-bed reactivity and longevity, which enabled a low catalystloading of 0.1 mol % Pd/C for nitro reduction on a multikilogram scale.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2839–2849"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Encouraging the Exploration of Nickel Catalysis in Pharmaceutical Manufacturing Processes: Lessons Learned during Catalyst Screening and Process Optimization for the Monoarylation of Ammonia","authors":"Xavier Caumes,&nbsp;Lu Han,&nbsp;Ruoxin Huang,&nbsp;Zhihua Zhu,&nbsp;Carin C. C. Johansson Seechurn,&nbsp;Alexander M. Kluwer","doi":"10.1021/acs.oprd.6c00122","DOIUrl":"10.1021/acs.oprd.6c00122","url":null,"abstract":"<p>Reports of new ligandsor precatalysts based on non-platinumgroupmetal (pgm) catalysis, as well as the number of publications describingnew methodology that relies on non-pgm catalysts, are at an all-timehigh. Catalyst screening groups and process chemists are now beginningto seriously investigate and evaluate non-pgm-based processes whencarrying out route scouting and process optimization. The million-dollarquestion is how many already established manufacturing processes andhow many launched drugs may have benefited from the use of non-pgmcatalysis, had it been available and considered at the time of processoptimization and launch? We wanted to explore one such example andidentified a previously reported palladium-catalyzed selective formalmonoarylation of ammonia, from the process used to make abemaciblib,as a suitable model reaction. This article describes our lessons learnedfrom evaluating this specific reaction in a high-throughput screeningstudy to identify a suitable nickel-based catalyst for the monoarylationof ammonia (NH₃), process optimization, and product isolationattempts. The preformed complex (NHP-DalPhos)Ni(<em>o</em>-tol)Cl) <strong>Cat5</strong> was identified as the best-performingcatalyst and provided the desired primary amine <strong>2</strong> in82% conversion. The DalPhos family of ligands has been proven to providegood reactivity in cases where other ligands have failed, and thereason behind this has so far only been partially understood. Crucially,as part of our study, a structure-activity relationship (SAR) modelbased on three distinct catalyst descriptors (buried volume, P–Ni–Pbond angle, and electron richness) was uncovered. This has previouslynot been described for nickel catalysis while being known in broadterms for palladium catalysis and could fill a gap as an up-until-nowmissing insight for the successful implementation of nickel-catalyzedreactions. Through this model, we achieved a better understandingof the ligand parameters that proved to be important for a highlyactive and selective catalyst. Overall, we expect that by sharingour lessons learned, our story can act as a trigger to encourage moreresearchers to evaluate nickel catalysis alongside palladium whileavoiding having to tackle the same issues we encountered, and thatthe SAR model can provide a useful tool to aid and accelerate theidentification of the most effective nickel catalyst by maximizingthe coverage of chemical space.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 10","pages":"2649–2660"},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}