1453851-57-4Relevant articles and documents
Kumada-Corriu Heteroaryl Cross-Coupling for Synthesis of a Pharmaceutical Intermediate: Comparison of Batch Versus Continuous Reaction Modes
Linghu, Xin,Wong, Nicholas,Jost, Vera,Fantasia, Serena,Sowell, C. Gregory,Gosselin, Francis
, p. 1320 - 1325 (2017)
Pyridone 1, a key intermediate in the preparation of ERK inhibitor GDC-0994, was synthesized via a cross-coupling/hydrolysis sequence from commercially available starting materials. C-C bond formation was achieved via an efficient palladium catalyzed Kumada-Corriu cross-coupling reaction. However, the 4-pyridylmagnesium halide reagent generated in situ was found to be unstable at the reaction temperature, leading to inconsistent results on scale. In order to address process robustness issues associated with the cross-coupling reaction, we investigated both flow chemistry and a low temperature Kumada-Corriu coupling reaction. Finally, a basic hydrolysis process of 2-fluoropyridine was developed to avoid formation of toxic and corrosive hydrofluoric acid, resulting in a safe and scalable process toward 1.
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
COMBINATION OF A MEK INHIBITOR AND AN ERK INHIBITOR FOR USE IN TREATMENT OF HYPERPROLIFERATIVE DISEASES
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Page/Page column 25, (2015/03/28)
The invention provides combinations comprising a MEK inhibitor (such as GDC-0973 or GDC-0623), or a pharmaceutically acceptable salt thereof and an ERK inhibitor (such as GDC-0994). The combinations are particularly useful for treating hyperproliferative disorders, such as cancer.
Discovery of highly potent, selective, and efficacious small molecule inhibitors of ERK1/2
Ren, Li,Grina, Jonas,Moreno, David,Blake, James F.,Gaudino, John J.,Garrey, Rustam,Metcalf, Andrew T.,Burkard, Michael,Martinson, Matthew,Rasor, Kevin,Chen, Huifen,Dean, Brian,Gould, Stephen E.,Pacheco, Patricia,Shahidi-Latham, Sheerin,Yin, Jianping,West, Kristina,Wang, Weiru,Moffat, John G.,Schwarz, Jacob B.
, p. 1976 - 1991 (2015/04/27)
Using structure-based design, a novel series of pyridone ERK1/2 inhibitors was developed. Optimization led to the identification of (S)-14k, a potent, selective, and orally bioavailable agent that inhibited tumor growth in mouse xenograft models. On the basis of its in vivo efficacy and preliminary safety profiles, (S)-14k was selected for further preclinical evaluation.
SERINE/THREONINE KINASE INHIBITORS
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Paragraph 00247, (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.
