1453848-26-4Relevant articles and documents
PROCESS FOR THE MANUFACTURING OF MEDICAMENTS
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, (2017/02/24)
The present invention provides a process for the manufacture of a compound of formula VIIIa and salts forms of VIIIa where Rc is an aryl sulfonic acid
Development of a Practical Synthesis of ERK Inhibitor GDC-0994
Linghu, Xin,Wong, Nicholas,Iding, Hans,Jost, Vera,Zhang, Haiming,Koenig, Stefan G.,Sowell, C. Gregory,Gosselin, Francis
, p. 387 - 398 (2017/03/24)
The process development of a synthetic route to manufacture ERK inhibitor GDC-0994 on multikilogram scale is reported herein. The API was prepared as the corresponding benzenesulfonate salt in 7 steps and 41% overall yield. The synthetic route features a biocatalytic asymmetric ketone reduction, a regioselective pyridone SN2 reaction, and a safe and scalable tungstate-catalyzed sulfide oxidation. The end-game process involves a telescoped SNAr/desilylation/benzenesulfonate salt formation sequence. Finally, the development of the API crystallization allowed purging of process-related impurities, obtaining >99.5A% HPLC and >99% ee of the target molecule.
Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development
Blake, James F.,Burkard, Michael,Chan, Jocelyn,Chen, Huifen,Chou, Kang-Jye,Diaz, Dolores,Dudley, Danette A.,Gaudino, John J.,Gould, Stephen E.,Grina, Jonas,Hunsaker, Thomas,Liu, Lichuan,Martinson, Matthew,Moreno, David,Mueller, Lars,Orr, Christine,Pacheco, Patricia,Qin, Ann,Rasor, Kevin,Ren, Li,Robarge, Kirk,Shahidi-Latham, Sheerin,Stults, Jeffrey,Sullivan, Francis,Wang, Weiru,Yin, Jianping,Zhou, Aihe,Belvin, Marcia,Merchant, Mark,Moffat, John,Schwarz, Jacob B.
, p. 5650 - 5660 (2016/07/06)
The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes
SERINE/THREONINE KINASE INHIBITORS
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, (2013/09/12)
Compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative, pain and inflammatory diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
