1375541-21-1Relevant articles and documents
Phase-Transfer-Catalyzed Asymmetric Annulations of Alkyl Dihalides with Oxindoles: Unified Access to Chiral Spirocarbocyclic Oxindoles
Gao, Min,Hu, Lin,Li, Xuemin,Li, Yongyi
supporting information, p. 875 - 880 (2022/02/05)
A general phase-transfer-catalyzed asymmetric (n+1) (n = 4 or 5) annulation reaction, featuring the direct coupling of simple oxindoles with alkyl dihalides that are allylic/benzylic and non-allylic/benzylic, has been developed to provide previously inacc
Practical Asymmetric Synthesis of a Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist Ubrogepant
Yasuda, Nobuyoshi,Cleator, Ed,Kosjek, Birgit,Yin, Jianguo,Xiang, Bangping,Chen, Frank,Kuo, Shen-Chun,Belyk, Kevin,Mullens, Peter R.,Goodyear, Adrian,Edwards, John S.,Bishop, Brian,Ceglia, Scott,Belardi, Justin,Tan, Lushi,Song, Zhiguo J.,Dimichele, Lisa,Reamer, Robert,Cabirol, Fabien L.,Tang, Weng Lin,Liu, Guiquan
, p. 1851 - 1858 (2017/11/24)
The development of a scalable asymmetric route to a new calcitonin gene-related peptide (CGRP) receptor antagonist is described. The synthesis of the two key fragments was redefined, and the intermediates were accessed through novel chemistry. Chiral lactam 2 was prepared by an enzyme mediated dynamic kinetic transamination which simultaneously set two stereocenters. Enzyme evolution resulted in an optimized transaminase providing the desired configuration in >60:1 syn/anti. The final chiral center was set via a crystallization induced diastereomeric transformation. The asymmetric spirocyclization to form the second fragment, chiral spiro acid intermediate 3, was catalyzed by a novel doubly quaternized phase transfer catalyst and provided optically pure material on isolation. With the two fragments in hand, development of their final union by amide bond formation and subsequent direct isolation is described. The described chemistry has been used to deliver over 100 kg of our desired target, ubrogepant.
PROCESS FOR MAKING CGRP RECEPTOR ANTAGONISTS
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, (2013/12/03)
The disclosure encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, having less steps and improved yields as compared to previous synthetic methods for making these compounds, which are CGRP receptor antagonists, useful for the treatment of migrane. Conditions for an amide bond formation between an acid and amine include for example reacting the compounds of Formulae B (after salt break) and C with an amide coupling reagent and optionally an additive and an acid and/or a base in a non-reactive solvent.