A generic liquid chromatography-mass spectrometry method for monitoring bis(pinacolato)diboron mutagenic impurity in pharmaceutical compounds

Lin, Ziqing; Tai, Hua-Chia; Petruzzella, Emanuele; Tang, Fei-Li; Ye, Yun K.; Chadwick, James; Ding, Wanyu; He, Brian Lingfeng; Miller, Scott A.

doi:10.1016/j.jcoa.2021.100009

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Cited by 3 publications

References 17 publications

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Applications of Biotechnology in Pharmaceutical Product Analysis

Aslam,

Rani,

Khan

et al. 2024

Interdisciplinary Biotechnological Advances

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Applications of Biotechnology in Pharmaceutical Product Analysis

Aslam,

Rani,

Khan

et al. 2024

Interdisciplinary Biotechnological Advances

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Recent developments in electromigration techniques related to pharmaceutical and biomedical analysis – A review

Fanali,

Della Posta,

Gentili

et al. 2023

Journal of Pharmaceutical and Biomedical Analysis

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Development of an Inherently Safe and Scalable Nickel-Catalyzed Borylation Process of an Aryl Sulfamate

Joannou,

Bemis,

Purdum

et al. 2024

Org. Process Res. Dev.

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A safe and scalable synthesis of A, a key aryl boronate ester intermediate toward an immunology asset udifitimod, via a Ni-catalyzed Miyaura borylation is reported. High-throughput experimentation, design of experiment, and reagent stability/ compatibility studies were used to optimize the reaction conditions and furnish the borylation of aryl sulfamate B in 80−85% yield and >98% purity/potency. Significant hydrogen off-gassing was observed during the reaction, metal remediation, and crystallization steps of the first-generation process, and efforts were made to quantify, understand, and mitigate this off-gassing to ensure a safe and reliable scale-up. Two multikilogram batches of the process were successfully run to afford A in an average 85% yield, >99% potency, and ≤28 ppm residual Ni. Using the mechanistic learnings from this work, a second-generation process was developed which significantly reduced hydrogen off-gassing at all steps of the process, as well as increasing final yield and reducing process mass intensity. This second-generation process was demonstrated on a 1 kg scale to afford the product in 90% yield, >99% purity/potency, and 50 ppm residual Ni.

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A generic liquid chromatography-mass spectrometry method for monitoring bis(pinacolato)diboron mutagenic impurity in pharmaceutical compounds

Cited by 3 publications

References 17 publications

Applications of Biotechnology in Pharmaceutical Product Analysis

Applications of Biotechnology in Pharmaceutical Product Analysis

Recent developments in electromigration techniques related to pharmaceutical and biomedical analysis – A review

Development of an Inherently Safe and Scalable Nickel-Catalyzed Borylation Process of an Aryl Sulfamate

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