946399-93-5

Basic information

• Product Name: (R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine
• Synonyms: (R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine
• CAS NO: 946399-93-5
• Molecular Weight: 528.376
• Mol File: 946399-93-5.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: (R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine(946399-93-5)
• EPA Substance Registry System: (R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine(946399-93-5)

Safety Data

• Hazardous Substances Data: 946399-93-5(Hazardous Substances Data)

Upstream product

• 75336-86-6 (2R)-methylpiperazine 
• 40161-55-5 1-bromo-4-fluoro-2-(trifluoromethyl)benzene 
• 946398-05-6 (2R)-1-[(3-bromophenyl)sulfonyl]-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazine 
• 73183-34-3 bis(pinacol)diborane 
• 946399-84-4 (3R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine 

Relevant articles and documents

Synthesis of potent and orally efficacious 11β-hydroxysteroid dehydrogenase type 1 inhibitor HSD-016

Cortisol and the glucocorticoid receptor (GR) signaling pathway has been linked to the development of diabetes and metabolic syndrome. In vivo, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to its active form, cortisol. Existing clinical data have supported 11β-HSD1 as a valid therapeutic target for type 2 diabetes. In our research program, (R)-1,1,1-trifluoro-2-(3-((R)-4-(4-fluoro-2- (trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)phenyl)propan-2-ol (HSD-016) was discovered to be a potent, selective, and efficacious 11β-HSD1 inhibitor and advanced as a clinical candidate. Herein, a reliable and scalable synthesis of HSD-016 is described. Key transformations include an asymmetric synthesis of a chiral tertiary alcohol via Sharpless dihydroxylation, epoxide formation, and subsequent mild reduction. This route ensured multikilogram quantities of HSD-016 necessary for clinical studies.