Chetan Padmakar Darne, Ning Li, Daniel Smith, Shasha Zhang, Premsai Rai Neithnadka, Arundutt Silamkoti, Arunachalam Arumugam, Anuradha Gupta, Zhenqiu Hong, Subramaniam Krishnananthan, Bei Wang, Rulin Zhao, Shiuhang Yip, Dauh-Rurng Wu, James Kempson, Deborah S. Mortensen, Arvind Mathur and Jianqing Li*,
{"title":"Development of a Safe and Practical Synthesis of Enantiomerically Pure (S)- and (R)-N-Boc-3-(Trifluoromethyl)piperazines Enabled by Aza-Michael Addition of Optically Pure 4-Phenyl-2-Oxazolidinone to 3,3,3-Trifluoro-1-Nitropropene","authors":"Chetan Padmakar Darne, Ning Li, Daniel Smith, Shasha Zhang, Premsai Rai Neithnadka, Arundutt Silamkoti, Arunachalam Arumugam, Anuradha Gupta, Zhenqiu Hong, Subramaniam Krishnananthan, Bei Wang, Rulin Zhao, Shiuhang Yip, Dauh-Rurng Wu, James Kempson, Deborah S. Mortensen, Arvind Mathur and Jianqing Li*, ","doi":"10.1021/acs.oprd.4c0028910.1021/acs.oprd.4c00289","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00289https://doi.org/10.1021/acs.oprd.4c00289","url":null,"abstract":"<p >(<i>S</i>)- and (<i>R</i>)-<i>N</i>-Boc-3-(trifluoromethyl)piperazines are attractive building blocks for the rational design of drugs. Until now, their chiral syntheses were unknown. Exploration of three synthetic approaches via chiral 3,3,3-trifluoropropane-1,2-diamines yielded a scalable route that has been used for multigram synthesis. Two routes were not amendable for scale-up due to low yielding, tedious purification, limited availability of reagents, and safety issues. The successful and practical route relied on a modified process to mitigate the safety issues for the synthesis of (<i>E</i>)-3,3,3-trifluoro-1-nitroprop-1-ene, which was used as a stock solution for the highly diastereoselective aza-Michael addition of optically pure 4-phenyl-2-oxazolidinone. Boc protection of an amino group allowed subsequent transformations to chiral <i>N</i>-Boc-protected 3,3,3-trifluoropropane-1,2-diamine under mild conditions, without the need for chiral chromatography. The amidation of chiral <i>N</i>-Boc-protected 3,3,3-trifluoropropane-1,2-diamine with 2-chloroacetyl chloride, followed by intramolecular cyclization and subsequent reduction afforded enantiomerically pure <i>N</i>-Boc-3-(trifluoromethyl)piperazines.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990172","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}
Fangkun Zhang, Aozhe Meng, Yan Long, Zai-Qun Yu, Shuai Yu, Baoming Shan, Xue Z. Wang and Qilei Xu*,
{"title":"Advances and Opportunities Concerning Nucleation Measurement and Control Technology in Crystallization","authors":"Fangkun Zhang, Aozhe Meng, Yan Long, Zai-Qun Yu, Shuai Yu, Baoming Shan, Xue Z. Wang and Qilei Xu*, ","doi":"10.1021/acs.oprd.4c0018210.1021/acs.oprd.4c00182","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00182https://doi.org/10.1021/acs.oprd.4c00182","url":null,"abstract":"<p >Nucleation as a unique phenomenon in the crystallization process has always been a hot topic. With the development of nucleation theory and process analysis technology (PAT), nucleation control technology (NCT) has been widely applied in industrial crystallization processes. This paper provides a comprehensive review of advancements in nucleation measurement and control technologies within crystallization processes, systematically analyzing the principles, advantages, disadvantages, and application scopes of various NCTs, and particularly the factors affecting nucleation and nucleation-assisted technologies, including ultrasound, gassing, and membranes, are elaborated. These technologies are crucial for managing the unpredictable nature of nucleation to improve the consistency and quality of crystalline products. These advanced or novel control technologies are very attractive in providing continuous and stable high-purity seeds without externally adding additional seeds and have proven to be effective alternative methods for generating internal seeds. In addition, the challenges and opportunities were pointed out from the stability, controllability, and consistency of nucleation to promoting the efficient development of crystallization technology. NCTs play a vital role in industrial applications by ensuring control over the size, purity, and morphology of crystals. This review also explains the application of NCTs in industrial scenarios, positioning these technologies as essential for the advancement of various industrial applications.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990210","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}
Rosaria Ciriminna, Cristina Della Pina, Rafael Luque* and Mario Pagliaro*,
{"title":"Reshoring Fine Chemical and Pharmaceutical Productions","authors":"Rosaria Ciriminna, Cristina Della Pina, Rafael Luque* and Mario Pagliaro*, ","doi":"10.1021/acs.oprd.4c0021910.1021/acs.oprd.4c00219","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00219https://doi.org/10.1021/acs.oprd.4c00219","url":null,"abstract":"<p >Prolonged shortage of active pharmaceutical ingredients (APIs) in many countries that do not produce critically important APIs requires urgent reshoring of the said fine chemical productions. The situation is even worsened by frequent disruption of the global supply chains, first during the COVID-19 crisis and subsequently with the ongoing Red Sea crisis. In this study, we first outline the main economic and policy aspects emerging from selected cases of reshoring of API production to Europe. Hence, broadening the analysis to include selected cases in China and India, we investigate the industrial uptake of continuous manufacturing in fine chemicals production. Following said concrete analysis of the concrete situation, the study concludes with three main findings.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990169","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}
Rupanjali Prasad, Stefani Kocevska, Dimitri Skliar, Martha A. Grover* and Ronald W. Rousseau,
{"title":"Characterization, Solubility, and Hygroscopicity of BMS-817399","authors":"Rupanjali Prasad, Stefani Kocevska, Dimitri Skliar, Martha A. Grover* and Ronald W. Rousseau, ","doi":"10.1021/acs.oprd.3c0050110.1021/acs.oprd.3c00501","DOIUrl":"https://doi.org/10.1021/acs.oprd.3c00501https://doi.org/10.1021/acs.oprd.3c00501","url":null,"abstract":"<p >Characteristics of BMS-817399 that could influence the potential utility of the compound as an active pharmaceutical ingredient (API) have been explored. The compound exists as a monohydrate (Form 1) but is physically unstable as its crystal structure changes with variations in relative humidity and temperature. Thus, identifying a form that remains physically stable under fluctuating conditions of relative humidity was the objective of this work. Solubilities of Form 1 in ethanol, isopropanol, acetone, and acetonitrile were obtained using a Crystal16 apparatus, but recrystallization only occurred when the solvent was acetonitrile. X-ray diffraction (XRD) of solids obtained from recrystallization in the Crystal16 apparatus and from larger-scale experiments confirmed the existence of a new form (Form 2) of the compound. Solubilities of Form 2 were subsequently determined by using the Crystal16 apparatus. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed Form 1 as a monohydrate and showed that Form 2 is anhydrous. Dynamic vapor sorption was used to show that the water content of Form 1 varied with the relative humidity. Form 2 also became hygroscopic at elevated relative humidity, but XRD measurements confirmed that it exhibited physical stability.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.oprd.3c00501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chetan Padmakar Darne, Ning Li, Daniel Smith, Shasha Zhang, Premsai Rai Neithnadka, Arundutt Silamkoti, Arunachalam Arumugam, Anuradha Gupta, Zhenqiu Hong, Subramaniam Krishnananthan, Bei Wang, Rulin Zhao, Shiuhang Yip, Dauh-Rurng Wu, James Kempson, Deborah S. Mortensen, Arvind Mathur, Jianqing Li
{"title":"Development of a Safe and Practical Synthesis of Enantiomerically Pure (S)- and (R)-N-Boc-3-(Trifluoromethyl)piperazines Enabled by Aza-Michael Addition of Optically Pure 4-Phenyl-2-Oxazolidinone to 3,3,3-Trifluoro-1-Nitropropene","authors":"Chetan Padmakar Darne, Ning Li, Daniel Smith, Shasha Zhang, Premsai Rai Neithnadka, Arundutt Silamkoti, Arunachalam Arumugam, Anuradha Gupta, Zhenqiu Hong, Subramaniam Krishnananthan, Bei Wang, Rulin Zhao, Shiuhang Yip, Dauh-Rurng Wu, James Kempson, Deborah S. Mortensen, Arvind Mathur, Jianqing Li","doi":"10.1021/acs.oprd.4c00289","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00289","url":null,"abstract":"(<i>S</i>)- and (<i>R</i>)-<i>N</i>-Boc-3-(trifluoromethyl)piperazines are attractive building blocks for the rational design of drugs. Until now, their chiral syntheses were unknown. Exploration of three synthetic approaches via chiral 3,3,3-trifluoropropane-1,2-diamines yielded a scalable route that has been used for multigram synthesis. Two routes were not amendable for scale-up due to low yielding, tedious purification, limited availability of reagents, and safety issues. The successful and practical route relied on a modified process to mitigate the safety issues for the synthesis of (<i>E</i>)-3,3,3-trifluoro-1-nitroprop-1-ene, which was used as a stock solution for the highly diastereoselective aza-Michael addition of optically pure 4-phenyl-2-oxazolidinone. Boc protection of an amino group allowed subsequent transformations to chiral <i>N</i>-Boc-protected 3,3,3-trifluoropropane-1,2-diamine under mild conditions, without the need for chiral chromatography. The amidation of chiral <i>N</i>-Boc-protected 3,3,3-trifluoropropane-1,2-diamine with 2-chloroacetyl chloride, followed by intramolecular cyclization and subsequent reduction afforded enantiomerically pure <i>N</i>-Boc-3-(trifluoromethyl)piperazines.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877429","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}
Fangkun Zhang, Aozhe Meng, Yan Long, Zai-Qun Yu, Shuai Yu, Baoming Shan, Xue Z. Wang, Qilei Xu
{"title":"Advances and Opportunities Concerning Nucleation Measurement and Control Technology in Crystallization","authors":"Fangkun Zhang, Aozhe Meng, Yan Long, Zai-Qun Yu, Shuai Yu, Baoming Shan, Xue Z. Wang, Qilei Xu","doi":"10.1021/acs.oprd.4c00182","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00182","url":null,"abstract":"Nucleation as a unique phenomenon in the crystallization process has always been a hot topic. With the development of nucleation theory and process analysis technology (PAT), nucleation control technology (NCT) has been widely applied in industrial crystallization processes. This paper provides a comprehensive review of advancements in nucleation measurement and control technologies within crystallization processes, systematically analyzing the principles, advantages, disadvantages, and application scopes of various NCTs, and particularly the factors affecting nucleation and nucleation-assisted technologies, including ultrasound, gassing, and membranes, are elaborated. These technologies are crucial for managing the unpredictable nature of nucleation to improve the consistency and quality of crystalline products. These advanced or novel control technologies are very attractive in providing continuous and stable high-purity seeds without externally adding additional seeds and have proven to be effective alternative methods for generating internal seeds. In addition, the challenges and opportunities were pointed out from the stability, controllability, and consistency of nucleation to promoting the efficient development of crystallization technology. NCTs play a vital role in industrial applications by ensuring control over the size, purity, and morphology of crystals. This review also explains the application of NCTs in industrial scenarios, positioning these technologies as essential for the advancement of various industrial applications.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858140","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}
Rupanjali Prasad, Stefani Kocevska, Dimitri Skliar, Martha A. Grover, Ronald W. Rousseau
{"title":"Characterization, Solubility, and Hygroscopicity of BMS-817399","authors":"Rupanjali Prasad, Stefani Kocevska, Dimitri Skliar, Martha A. Grover, Ronald W. Rousseau","doi":"10.1021/acs.oprd.3c00501","DOIUrl":"https://doi.org/10.1021/acs.oprd.3c00501","url":null,"abstract":"Characteristics of BMS-817399 that could influence the potential utility of the compound as an active pharmaceutical ingredient (API) have been explored. The compound exists as a monohydrate (Form 1) but is physically unstable as its crystal structure changes with variations in relative humidity and temperature. Thus, identifying a form that remains physically stable under fluctuating conditions of relative humidity was the objective of this work. Solubilities of Form 1 in ethanol, isopropanol, acetone, and acetonitrile were obtained using a Crystal16 apparatus, but recrystallization only occurred when the solvent was acetonitrile. X-ray diffraction (XRD) of solids obtained from recrystallization in the Crystal16 apparatus and from larger-scale experiments confirmed the existence of a new form (Form 2) of the compound. Solubilities of Form 2 were subsequently determined by using the Crystal16 apparatus. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed Form 1 as a monohydrate and showed that Form 2 is anhydrous. Dynamic vapor sorption was used to show that the water content of Form 1 varied with the relative humidity. Form 2 also became hygroscopic at elevated relative humidity, but XRD measurements confirmed that it exhibited physical stability.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858139","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}
Paul G. Bulger*, Michael T. Jones, J. Gair Ford, Kate Schrier, Kevin P. Cole, Frank Bernardoni, Olivier Dirat, Qunying Zhang, Osama Chahrour, Joy Miller, Llorente Bonaga, Andrew T. Parsons and Lan Yang,
{"title":"Risk Assessment and Control of N-Nitrosamines in Antibody–Drug Conjugates: Current Industry Practices","authors":"Paul G. Bulger*, Michael T. Jones, J. Gair Ford, Kate Schrier, Kevin P. Cole, Frank Bernardoni, Olivier Dirat, Qunying Zhang, Osama Chahrour, Joy Miller, Llorente Bonaga, Andrew T. Parsons and Lan Yang, ","doi":"10.1021/acs.oprd.4c0025410.1021/acs.oprd.4c00254","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00254https://doi.org/10.1021/acs.oprd.4c00254","url":null,"abstract":"<p >Antibody–drug conjugates (ADCs) and <i>N</i>-nitrosamines are two topics that have seen a surge of interest in recent years. ADCs are increasingly prevalent as oncology therapeutics in clinical development and on the market. Concerns about the potential presence of <i>N</i>-nitrosamines in pharmaceutical products have led to increased regulatory scrutiny and implementation of robust control strategies by the industry. This article, the first in a two-part series, provides visibility into current industry practices for risk assessment and control of <i>N</i>-nitrosamines in ADCs with results and analysis from a benchmarking survey of member companies of the IQ Consortium. Items covered include assessment methodology, identification and characterization of risks, control limits at the drug-linker intermediate and drug substance, and specific factors related to the ADC modality that can be considered. Simpler <i>N</i>-nitrosamines (e.g., NDMA) and more complex <i>N</i>-nitrosamine drug-linker-related impurities (NDLRIs) are discussed. Areas where there are greater or lesser degrees of consistency across companies are highlighted. The second paper builds on these survey results by presenting a comprehensive set of recommendations for the risk evaluation and control strategy of <i>N</i>-nitrosamine impurities in drug-linkers and ADCs. Taken together, these papers provide a perspective on the current state and encourage further development of scientifically sound approaches in this field.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990209","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}
Paul G. Bulger, Michael T. Jones, J. Gair Ford, Kate Schrier, Kevin P. Cole, Frank Bernardoni, Olivier Dirat, Qunying Zhang, Osama Chahrour, Joy Miller, Llorente Bonaga, Andrew T. Parsons, Lan Yang
{"title":"Risk Assessment and Control of N-Nitrosamines in Antibody–Drug Conjugates: Current Industry Practices","authors":"Paul G. Bulger, Michael T. Jones, J. Gair Ford, Kate Schrier, Kevin P. Cole, Frank Bernardoni, Olivier Dirat, Qunying Zhang, Osama Chahrour, Joy Miller, Llorente Bonaga, Andrew T. Parsons, Lan Yang","doi":"10.1021/acs.oprd.4c00254","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00254","url":null,"abstract":"Antibody–drug conjugates (ADCs) and <i>N</i>-nitrosamines are two topics that have seen a surge of interest in recent years. ADCs are increasingly prevalent as oncology therapeutics in clinical development and on the market. Concerns about the potential presence of <i>N</i>-nitrosamines in pharmaceutical products have led to increased regulatory scrutiny and implementation of robust control strategies by the industry. This article, the first in a two-part series, provides visibility into current industry practices for risk assessment and control of <i>N</i>-nitrosamines in ADCs with results and analysis from a benchmarking survey of member companies of the IQ Consortium. Items covered include assessment methodology, identification and characterization of risks, control limits at the drug-linker intermediate and drug substance, and specific factors related to the ADC modality that can be considered. Simpler <i>N</i>-nitrosamines (e.g., NDMA) and more complex <i>N</i>-nitrosamine drug-linker-related impurities (NDLRIs) are discussed. Areas where there are greater or lesser degrees of consistency across companies are highlighted. The second paper builds on these survey results by presenting a comprehensive set of recommendations for the risk evaluation and control strategy of <i>N</i>-nitrosamine impurities in drug-linkers and ADCs. Taken together, these papers provide a perspective on the current state and encourage further development of scientifically sound approaches in this field.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877772","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}
George Karageorgis*, James J. Douglas and Gareth P. Howell,
{"title":"Analysis of the Change in Molecular Complexity of Reaction Products in Process Development Activities at AstraZeneca Over Time","authors":"George Karageorgis*, James J. Douglas and Gareth P. Howell, ","doi":"10.1021/acs.oprd.4c0022410.1021/acs.oprd.4c00224","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00224https://doi.org/10.1021/acs.oprd.4c00224","url":null,"abstract":"<p >The assessment of molecular complexity of active pharmaceutical ingredients (APIs) can help guide decisions within drug development, for example, by correlation to sustainability targets, project resource requirements, and predicted development and manufacturing timelines. However, such quantifications are limited by the challenge of defining complexity itself as well as the small sample size of API molecules making longer term comparisons challenging. We have used four complementary approaches to calculate the complexity of reaction products of more than 165,000 reaction entries across our process development electronic laboratory notebooks. Importantly, this dataset covers both intermediates, APIs, and other molecules requiring synthesis, thus, attempts to provide an analysis of reaction products from all our synthetic chemistry activities. This information facilitated the investigation of changes in the mean values of different measures of molecular complexity per year between 2007 and 2020. We discuss the insights these quantifications reveal and how this analysis may be of more general use in understanding the diversity of the molecules in our process development portfolio.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990254","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}