Development of a Scalable Synthesis for the Potent Kinase Inhibitor BMS-986236; 1-(5-(4-(3-Hydroxy-3-methylbutyl)-1H-1,2,3-triazol-1-yl)-4-(isopropylamino)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile

Arunachalam, Pirama Nayagam; Kuppusamy, Prakasam; Ganesan, Sivakumar; Krishnamoorthy, Suresh; Nimje, Roshan Y.; Jarugu, Lokesh Babu; Chikkananjaiah, Nanjundaswamy Kanikahalli; Reddy, China Anki; Anjanappa, Prakash; Botlagunta, Murali; Vanteru, Sridhar; Maddala, Nageswararao; Shankar, Muniyappa; Nair, Satheesh K.; Hynes, John; Santella, Joseph B.; Carter, Percy H.; Rampulla, Richard; Vetrichelvan, Muthalagu; Gupta, Anuradha; Gupta, Arun Kumar; Mathur, Arvind

doi:10.1021/acs.oprd.9b00023

Cited by 6 publications

(2 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to the material in entry 9, this material is ranked as either Low Hazard or Medium Hazard, depending on the scale. Scientists at Bristol Myers Squibb (BMS) reported the use of 5-azido-2-chloro- N -isopropylpyridin-4-amine (entry 11) in the synthesis of a kinase inhibitor . Although no ARC or explosivity data were provided in the article, this tool would have highlighted the need for such testing.…”

Section: Applying the Oreos Methodsmentioning

confidence: 99%

Explosive Hazard Identification in Pharmaceutical Process Development: A Novel Screening Method and Workflow for Shipping Potentially Explosive Materials

Sperry

Azuma

Stone

2021

Org. Process Res. Dev.

View full text Add to dashboard Cite

When a material is identified as potentially capable of explosive propagation by the Yoshida correlation, process safety scientists have few options for semiquantitatively assessing the hazards associated with the use of that material. Oxygen balance calculations, the Rule of 6, and the United Nations (U.N.) explosive functional group list are commonly employed qualitative/semiquantitative methods to assess explosivity without requiring additional experimental data. In contrast, a full United Nations Transportation of Dangerous Goods testing regimen requires, at a minimum, 2 kg of material for Test Series 1 alone, an excessive amount that is rarely available in early pharmaceutical development. A new assessment, called the O.R.E.O.S. method, has been developed that combines the three traditional methods for screening of explosive properties (Oxygen balance calculations, the Rule of 6, and the Explosive functional group list) with the Onset of decomposition determined by differential scanning calorimetry and the proposed Scale. This new assessment has been applied to known energetic materials that are flagged as potentially capable of explosive propagation by the Yoshida correlation and has been shown to be effective at classifying materials in a scale-dependent manner. The tool is customizable to fit any organization’s internal guidance on handling energetic materials. This assessment should find wide utility in both pharmaceutical development groups and contract research organizations as a means to classify compounds that may require further testing before scale-up or to steer project teams to discover safer alternatives. A brief description of the challenges associated with transporting materials for U.N. Series Testing is also presented with the aim of demystifying the process for obtaining such valuable data.

show abstract

Section: Applying the Oreos Methodsmentioning

confidence: 99%

Explosive Hazard Identification in Pharmaceutical Process Development: A Novel Screening Method and Workflow for Shipping Potentially Explosive Materials

Sperry

Azuma

Stone

2021

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…Indeed, a 53% yield of the 5,6-fused heterocycle 3p was obtained in one step from commercial starting materials (Scheme 3). Finally, a tangible application of this reaction in the preparation of an intermediate leading to the IRAK4 inhibitor BMS-986236 23 was examined to highlight the advantages of this azide-free method (Scheme 4). The first-generation synthesis of BMS-986236 used an energetic azide intermediate, necessitating a second-generation synthesis for scale-up that used a less-energetic hetaryl azide.…”

Section: Letter Syn Lettmentioning

confidence: 99%

One-Pot, Metal- and Azide-Free Synthesis of 1,2,3-Triazoles from α-Ketoacetals and Amines

Zehnder

Hawkins

Sutton

2019

Synlett

View full text Add to dashboard Cite

show abstract

Prinzipien der Syntheseplanung

Düfert¹

2023

Organische Synthesemethoden

View full text Add to dashboard Cite

Development of a Scalable Synthesis for the Potent Kinase Inhibitor BMS-986236; 1-(5-(4-(3-Hydroxy-3-methylbutyl)-1H-1,2,3-triazol-1-yl)-4-(isopropylamino)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile

Abstract: Development of a Scalable Synthesis for the Potent Kinase Inhibitor BMS-986236; 1-(5-(4-(3-Hydroxy-3-methylbutyl)-1H-1,2,3-triazol-1yl)-4-(isopropylamino)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine-5carbonitrile

Cited by 6 publications

References 26 publications

Explosive Hazard Identification in Pharmaceutical Process Development: A Novel Screening Method and Workflow for Shipping Potentially Explosive Materials

Explosive Hazard Identification in Pharmaceutical Process Development: A Novel Screening Method and Workflow for Shipping Potentially Explosive Materials

One-Pot, Metal- and Azide-Free Synthesis of 1,2,3-Triazoles from α-Ketoacetals and Amines

Prinzipien der Syntheseplanung

Contact Info

Product

Resources

About