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
A scalable route to 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 (1, BMS-986236) was developed by incorporating an alternate azide intermediate following safety-driven processes. The newly developed process invo...
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| Veröffentlicht in: | Organic process research & development 2019-05, Vol.23 (5), p.912-918 |
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| creator | Arunachalam, Pirama Nayagam Kuppusamy, Prakasam Ganesan, Sivakumar Krishnamoorthy, Suresh Nimje, Roshan Y Jarugu, Lokesh Babu Kanikahalli Chikkananjaiah, Nanjundaswamy Anki Reddy, China Anjanappa, Prakash Botlagunta, Murali Vanteru, Sridhar Maddala, Nageswararao Shankar, Muniyappa Nair, Satheesh Hynes, John Santella, Joseph B Carter, Percy H Rampulla, Richard Vetrichelvan, Muthalagu Gupta, Anuradha Gupta, Arun Kumar Mathur, Arvind |
| description | A scalable route to 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 (1, BMS-986236) was developed by incorporating an alternate azide intermediate following safety-driven processes. The newly developed process involved mitigating safety hazards and eliminating the column chromatography purification. The issue of trace metal contamination in the final API observed in the first-generation synthesis has been overcome. |
| doi_str_mv | 10.1021/acs.oprd.9b00023 |
| format | Article |
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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</atitle><jtitle>Organic process research & development</jtitle><addtitle>Org. Process Res. Dev</addtitle><date>2019-05-17</date><risdate>2019</risdate><volume>23</volume><issue>5</issue><spage>912</spage><epage>918</epage><pages>912-918</pages><issn>1083-6160</issn><eissn>1520-586X</eissn><abstract>A scalable route to 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 (1, BMS-986236) was developed by incorporating an alternate azide intermediate following safety-driven processes. The newly developed process involved mitigating safety hazards and eliminating the column chromatography purification. The issue of trace metal contamination in the final API observed in the first-generation synthesis has been overcome.</abstract><pub>American Chemical Society</pub><doi>10.1021/acs.oprd.9b00023</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-5880-1164</orcidid><orcidid>https://orcid.org/0000-0001-7201-4143</orcidid><orcidid>https://orcid.org/0000-0002-4211-1441</orcidid></addata></record> |
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| source | ACS Publications |
| title | 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 |
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