1453851-59-6

Basic information

• Product Name: (R)-2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl methanesulfonate
• Synonyms: (R)-2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl methanesulfonate
• CAS NO: 1453851-59-6
• Molecular Weight: 382.956
• Mol File: 1453851-59-6.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: (R)-2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl methanesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl methanesulfonate(1453851-59-6)
• EPA Substance Registry System: (R)-2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl methanesulfonate(1453851-59-6)

Safety Data

• Hazardous Substances Data: 1453851-59-6(Hazardous Substances Data)

Upstream product

• 60811-18-9 2-chloro-5-bromofluorobenzene 
• 1395078-43-9 (R)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethanol 
• 124-63-0 methanesulfonyl chloride 
• 1453854-84-6 (R)-1-(4-chloro-3-fluorophenyl)ethane-1,2-diol 
• 1263414-46-5 1-chloro-2-fluoro-4-vinylbenzene 

Downstream Products

• 1453852-63-5 (S)-2-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-5-iodopyridazin-3(2H)-one 
• 1453853-08-1 (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-5-fluoro-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453853-16-1 (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-3-fluoro-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453852-36-2 (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453847-30-7 (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2( 1H)-one 
• 1453852-38-4 1-((S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((3S,4S)-3-fluorotetrahydro-2H-pyran-4-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453847-36-3 1-((S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-(((3S,4S)-3-fluorotetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2( 1H)-one 
• 1453847-59-0 (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453852-65-7 (S)-2-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-5-(2-(methylthio)pyrimidin-4-yl)pyridazin-3(2H)-one 
• 1453853-24-1 (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((2-methylpyrimidin-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453848-03-7 (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((2-methylpyrimidin-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453853-26-3 (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((2-methylpyridin-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453848-09-3 (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((2-methylpyridin-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453853-28-5 (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(( 1,3-dimethyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one 

Relevant articles and documents

Development of a Practical Synthesis of ERK Inhibitor GDC-0994

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.

COMBINATION OF A MEK INHIBITOR AND AN ERK INHIBITOR FOR USE IN TREATMENT OF HYPERPROLIFERATIVE DISEASES

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.

SERINE/THREONINE KINASE INHIBITORS

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.