1190363-46-2Relevant articles and documents
Development of a scalable palladium-catalyzed α-arylation process for the synthesis of a CGRP antagonist
Desai, Lopa V.,Hay, Michael B.,Leahy, David K.,Wei, Carolyn,Fanfair, Dayne,Rosner, Thorsten,Hsiao, Yi
, p. 5677 - 5684 (2013/07/11)
The Pd-catalyzed α-arylation of cycloheptapyridyl ketone is a key complexity-building step in the synthesis of BMS-846372, a CGRP antagonist. A first-generation process utilized Pd(OAc)2/PtBu 3·HBF4 catalyst system with a strong base NaO tBu. Although this process was demonstrated on multi-kilo scale, the harsh conditions led to non-selective metal catalyzed processes, which generated several operational, quality, and throughput issues. By acquiring detailed knowledge around several important process parameters, we were able to design an efficient and scalable second-generation α-arylation process using a Pd(OAc)2/RuPhos catalyst system with the weaker base, K 3PO4 in tert-amyl alcohol. This new weak base process was high yielding, efficient, and superior in several respects compared to the strong base process. The strategy behind the reaction and isolation development and the process considerations important to scaling a catalytic reaction from laboratory to manufacturing scale will be discussed.
CGRP Receptor Antagonists
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Page/Page column 31, (2009/10/21)
The disclosure generally relates to the novel compounds of formula I, including their salts, which are CGRP receptor antagonists. The disclosure also relates to pharmaceutical compositions and methods for using the compounds in the treatment of CGRP related disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD).
