543745-11-5

Basic information

• Product Name: 1-(3-cyano-4-fluoro)phenyl-3-trifluoromethyl-6-(4-iodo)phenyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one
• Synonyms: 1-(3-cyano-4-fluoro)phenyl-3-trifluoromethyl-6-(4-iodo)phenyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one
• CAS NO: 543745-11-5
• Molecular Weight: 526.232
• Mol File: 543745-11-5.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: 1-(3-cyano-4-fluoro)phenyl-3-trifluoromethyl-6-(4-iodo)phenyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(3-cyano-4-fluoro)phenyl-3-trifluoromethyl-6-(4-iodo)phenyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one(543745-11-5)
• EPA Substance Registry System: 1-(3-cyano-4-fluoro)phenyl-3-trifluoromethyl-6-(4-iodo)phenyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one(543745-11-5)

Safety Data

• Hazardous Substances Data: 543745-11-5(Hazardous Substances Data)

Upstream product

• 536759-87-2 1-(4-iodophenyl)-3-(4-morpholinyl)-4-(trifluoroacetyl)-5,6-dihydro-2(1H)-pyridinone 
• 280120-91-4 2-fluoro-5-hydrazinobenzonitrile hydrochloride 
• 540-37-4 p-aminoiodobenzene 
• 53312-81-5 3-cyano-4-fluoroaniline 
• 4509-90-4 5-bromovaleroyl chloride 
• 473927-69-4 1-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one 
• 545445-10-1 3,3-dichloro-1-(4-iodophenyl)-piperidin-2-one 
• 385425-15-0 1-(2-oxopiperidin-1-yl)-4-iodobenzene 
• 385425-14-9 1-(4-iodophenyl)-4-(2,2,2-trifluoroacetyl)-piperidine-2,3-dione 
• 161886-21-1 2-fluoro-5-hydrazinobenzonitrile 

Downstream Products

• 280118-23-2 1-(3-amino-benzo[d]isoxazol-5-yl)-6-[2'-(3-hydroxy-pyrrolidin-1-ylmethyl)-biphenyl-4-yl]-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one 
• 280118-23-2 BMS-740808 
• 543745-12-6 1-(3-Cyano-4-fluoro)phenyl-3-trifluoromethyl-6-[4-(2-formyl)phenyl]phenyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one 

Relevant articles and documents

1-[3-Aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[2′-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1′]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa

Attempts to further optimize the pyrazole factor Xa inhibitors centered on masking the aryl aniline P4 moiety. Scaffold optimization resulted in the identification of a novel bicyclic pyrazolo-pyridinone scaffold which retained fXa potency. The novel bicyclic scaffold preserved all binding interactions observed with the monocyclic counterpart and importantly the carboxamido moiety was integrated within the scaffold making it less susceptible to hydrolysis. These efforts led to the identification of 1-[3-aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[2′-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1′]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one 6f (BMS-740808), a highly potent (fXa Ki = 30 pM) with a rapid onset of inhibition (2.7 × 107 M-1 s-1) in vitro, selective (>1000-fold over other proteases), efficacious in the AVShunt thrombosis model, and orally bioavailable inhibitor of blood coagulation factor Xa.

Synthesis of 4,5-dihydro-pyrazolo [3,4-c] pyrid-2-ones

A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described. These compounds are useful as factor Xa inhibitors.