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The Development of a Robust Process for a CRF1 Receptor Antagonist

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Process Research and Development, Bristol-Myers Squibb Company P.O. Box 191, New Brunswick, New Jersey 08903, United States
Cite this: Org. Process Res. Dev. 2011, 15, 2, 343–352
Publication Date (Web):January 31, 2011
https://doi.org/10.1021/op100270u
Copyright © 2011 American Chemical Society

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    Abstract

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    A scalable and robust process was developed for the preparation of pexacerfont (2), a pyrazolotriazine corticotropin-releasing factor receptor 1 antagonist (CRF1). The formation of the core hydroxypyrazolotriazine moiety was achieved through two consecutive cyclizations of a semicarbazide, employing reaction conditions that are significantly milder than those reported in the literature. Further conversion to the key chloropyrazolotriazine intermediate was accomplished through a novel catalytic process using phosphorous oxychloride as the chlorinating agent. The active pharmaceutical ingredient 2 was obtained in >99.5% purity with a 68% overall yield for the six synthetic steps.

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