218301-47-4

Basic information

• Product Name: 2-FLUORO-5-(5-FURAN-2-YL-3-TRIFLUORO-METHYL-PYRAZOL-1-YL)-BENZONITRILE
• Synonyms: 2-FLUORO-5-(5-FURAN-2-YL-3-TRIFLUORO-METHYL-PYRAZOL-1-YL)-BENZONITRILE
• CAS NO: 218301-47-4
• Molecular Formula: C₁₅H₇F₄N₃O
• Molecular Weight: 321.2291928
• Mol File: 218301-47-4.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 2-FLUORO-5-(5-FURAN-2-YL-3-TRIFLUORO-METHYL-PYRAZOL-1-YL)-BENZONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-FLUORO-5-(5-FURAN-2-YL-3-TRIFLUORO-METHYL-PYRAZOL-1-YL)-BENZONITRILE(218301-47-4)
• EPA Substance Registry System: 2-FLUORO-5-(5-FURAN-2-YL-3-TRIFLUORO-METHYL-PYRAZOL-1-YL)-BENZONITRILE(218301-47-4)

Safety Data

• Hazardous Substances Data: 218301-47-4(Hazardous Substances Data)

Upstream product

• 557-21-1 dicyanozinc 
• 326-90-9 4,4,4-trifluoro-1-(2-furanyl)-1,3-butanedione 
• 53312-81-5 3-cyano-4-fluoroaniline 
• 17417-09-3 2-fluoro-5-nitrobenzonitrile 

Downstream Products

• 754193-45-8 2-(3-cyano-4-fluoro-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carbonyl chloride 
• 218301-83-8 methyl 1-(4'-fluoro-3'-cyanophenyl)-3-trifluoromethyl-5-pyrazolecarboxylic acid ester 
• 218301-84-9 methyl 1-(4'-isopropylideneaminooxy-3'-cyanophenyl)-3-trifluoromethyl-5-pyrazolecarboxylic acid ester 
• 335275-99-5 2-(3-cyano-4-fluorophenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (2-fluoro-4-iodophenyl)amide 
• 754193-49-2 1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-methyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide 
• 855869-83-9 2-(3-cyano-4-fluoro-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [2-methoxy-4-(2-methyl-imidazol-1-yl)-phenyl]-amide 
• 754193-51-6 1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-isopropyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide 
• 754193-50-5 1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-ethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide 
• 855869-81-7 2-(3-cyano-4-fluoro-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [2-cyano-4-(2-methyl-imidazol-1-yl)-phenyl]-amide 
• 855869-60-2 2-(3-cyano-4-fluoro-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (2-fluoro-4-morpholin-4-yl-phenyl)-amide 
• 855869-58-8 2-(3-cyano-4-fluoro-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [2-fluoro-4-(pyrrolidine-1-carbonyl)-phenyl]-amide 
• 405940-74-1 1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide 
• 540510-38-1 N-[4-(2-[hydroxymethyl]-1H-imidazol-1-yl)-2-fluorophenyl]-1-(3-amino-1,2-benzisoxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide 
• 209960-59-8 1-(3-cyano-4-fluorophenyl)-3-trifluoromethyl-5-[(3-fluoro-2'-methylsulfonyl-[1,1']-biphen-4-yl)aminocarbonyl]-pyrazole 

Relevant articles and documents

HUMAN PLASMA KALLIKREIN INHIBITORS

Disclosed are compounds of formula (I), as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one compound of the invention, and methods involving use of the compounds and compositions of the invention in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.

Discovery of 1-(3′-aminobenzisoxazol-5′-yl)-3-trifluoromethyl- N-[2-fluoro-4-[(2′-dimethylaminomethyl)imidazol-1-yl]phenyl] -1H-pyrazole-5-carboxyamide hydrochloride (razaxaban), a highly potent, selective, and orally bioavailable factor Xa inhibitor

Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P1 ligand resulted in compounds with improved selectivity for factor Xa relative to trypsin and plasma kallikrein. Further optimization of the P4 moiety led to compounds with enhanced permeability and reduced protein binding. The SAR and pharmacokinetic profile of this series of compounds is described herein. These efforts culminated in 1-(3′-aminobenzisoxazol-5′-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2′-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide (11d), a potent, selective, and orally bioavailable inhibitor of factor Xa. On the basis of its excellent in vitro potency and selectivity profile, high free fraction in human plasma, good oral bioavailability, and in vivo efficacy in antithrombotic models, the HCl salt of this compound was selected for clinical development as razaxaban (DPC 906, BMS-561389).

Novel N-[4- (1H-imidazol-1-yl) -2-fluorophenyl ] -3- (trifluoromethyl) -1H-pyrazole-5-carboxamides as factor Xa inhibitors

The present application describes N-[4-(1H-imidazol-1-yl)-2-fluorophenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamides and derivatives thereof of, which are useful as inhibitors of factor Xa.

Palladium-catalyzed cyanation reactions of aryl chlorides

We have discovered an efficient cyanation of aryl chlorides which employs Pd2(dba)3, dppf and Zn as the catalyst and Zn(CN)2 as the cyanide source. Both electron-deficient and electron-rich aryl chlorides are effectively cyanated under these conditions. This discovery represents the first successful palladium-catalyzed cyanation of both electron-deficient and electron-rich aryl chlorides. (C) 2000 DuPont Pharmaceuticals Company.