Development of a Concise Multikilogram Synthesis of LPA‑1 Antagonist BMS-986020 via a Tandem Borylation–Suzuki Procedure
The process development for the synthesis of BMS-986020 (1) via a palladium catalyzed tandem borylation/Suzuki reaction is described. Evaluation of conditions culminated in an efficient borylation procedure using tetrahydroxydiboron followed by a tandem Suzuki reaction employing the same commerciall...
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| Veröffentlicht in: | Organic process research & development 2017-11, Vol.21 (11), p.1859-1863 |
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| container_title | Organic process research & development |
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| creator | Smith, Michael J Lawler, Michael J Kopp, Nathaniel Mcleod, Douglas D Davulcu, Akin H Lin, Dong Katipally, Kishta Sfouggatakis, Chris |
| description | The process development for the synthesis of BMS-986020 (1) via a palladium catalyzed tandem borylation/Suzuki reaction is described. Evaluation of conditions culminated in an efficient borylation procedure using tetrahydroxydiboron followed by a tandem Suzuki reaction employing the same commercially available palladium catalyst for both steps. This methodology addressed shortcomings of early synthetic routes and was ultimately used for the multikilogram scale synthesis of the active pharmaceutical ingredient 1. Further evaluation of the borylation reaction showed useful reactivity with a range of substituted aryl bromides and iodides as coupling partners. These findings represent a practical, efficient, mild, and scalable method for borylation. |
| doi_str_mv | 10.1021/acs.oprd.7b00301 |
| format | Article |
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Process Res. Dev</addtitle><date>2017-11-17</date><risdate>2017</risdate><volume>21</volume><issue>11</issue><spage>1859</spage><epage>1863</epage><pages>1859-1863</pages><issn>1083-6160</issn><eissn>1520-586X</eissn><abstract>The process development for the synthesis of BMS-986020 (1) via a palladium catalyzed tandem borylation/Suzuki reaction is described. Evaluation of conditions culminated in an efficient borylation procedure using tetrahydroxydiboron followed by a tandem Suzuki reaction employing the same commercially available palladium catalyst for both steps. This methodology addressed shortcomings of early synthetic routes and was ultimately used for the multikilogram scale synthesis of the active pharmaceutical ingredient 1. Further evaluation of the borylation reaction showed useful reactivity with a range of substituted aryl bromides and iodides as coupling partners. 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| title | Development of a Concise Multikilogram Synthesis of LPA‑1 Antagonist BMS-986020 via a Tandem Borylation–Suzuki Procedure |
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