A Next Generation Synthesis of BACE1 Inhibitor Verubecestat (MK‑8931)

The development of a commercial manufacturing route to verubecestat (MK-8931) is described, highlights of which include the application of a continuous processing step to outcompete fast proton transfer in a Mannich-type ketimine addition, a copper-catalyzed amidation reaction, and an optimized guan...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Organic letters 2018-03, Vol.20 (6), p.1568-1571
Hauptverfasser:	Thaisrivongs, David A, Morris, William J, Tan, Lushi, Song, Zhiguo J, Lyons, Thomas W, Waldman, Jacob H, Naber, John R, Chen, Wenyong, Chen, Lu, Zhang, Baoyun, Yang, Jun
Format:	Artikel
Sprache:	eng
Schlagworte:	Amyloid Precursor Protein Secretases Aspartic Acid Endopeptidases Catalysis Copper Cyclic S-Oxides - chemical synthesis Enzyme Inhibitors Molecular Structure Thiadiazines - chemical synthesis
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	The development of a commercial manufacturing route to verubecestat (MK-8931) is described, highlights of which include the application of a continuous processing step to outcompete fast proton transfer in a Mannich-type ketimine addition, a copper-catalyzed amidation reaction, and an optimized guanidinylation procedure to form the key iminothiadiazine dioxide core.
ISSN:	1523-7060 1523-7052
DOI:	10.1021/acs.orglett.8b00259