515845-18-8Relevant academic research and scientific papers
Mild and Regioselective Synthesis of 3-CF3-Pyrazoles by the AgOTf-Catalysed Reaction of CF3-Ynones with Hydrazines
Topchiy, Maxim A.,Zharkova, Daria A.,Asachenko, Andrey F.,Muzalevskiy, Vasiliy M.,Chertkov, Vyacheslav A.,Nenajdenko, Valentine G.,Nechaev, Mikhail S.
supporting information, p. 3750 - 3755 (2018/07/31)
Gold- and silver-catalysed reactions of trifluoromethylated ynones with aryl (alkyl) hydrazines were investigated. The use of (THD-Dipp)AuOTf and AgOTf resulted in quick heterocyclization reactions to selectively give 3-CF3-pyrazoles. AgOTf was found to be the catalyst of choice, and various 3-CF3-pyrazoles were formed in up to 99 % isolated yield with high regioselectivity. The reaction has a broad scope: 3-CF3-pyrazoles with alkyl and aryl substituents as well as different functional groups can be prepared by this approach. The known pyrazole drugs Celebrex and SC-560 were efficiently prepared to demonstrate the utility of the method. Mechanistic investigations revealed that the reaction involves the formation of a hemiaminal as a key intermediate.
Selective, Metal-Free Approach to 3- or 5-CF3-Pyrazoles: Solvent Switchable Reaction of CF3-Ynones with Hydrazines
Muzalevskiy, Vasiliy M.,Rulev, Alexander Yu.,Romanov, Alexey R.,Kondrashov, Evgeniy V.,Ushakov, Igor A.,Chertkov, Vyacheslav A.,Nenajdenko, Valentine G.
, p. 7200 - 7214 (2017/07/26)
A detailed study of the reaction of trifluoroacetylated acetylenes and aryl (alkyl) hydrazines was performed, aimed to the regioselective synthesis of 3- or 5-trifluoromethylated pyrazoles. It was found that the regioselectivity of reaction depends dramatically on the solvent nature. Highly polar protic solvents (hexafluoroisopropanol) favor the formation of 3-trifluoromethylpyrazoles. In contrast, when the reaction was performed in polar aprotic solvents (DMSO), the formation of their 5-CF3-substituted isomers was preferentially observed. Alternatively, the regioselective assembly of 3-CF3-substituted pyrazoles can be performed via two-step one-pot procedure. The reaction of trifluoromethylated ynones with aryl (alkyl) hydrazines in the presence of acidic catalysts leads to formation of the corresponding hydrazones. The latter can be smoothly transformed into 3-CF3-pyrazoles by treatment with a base. This solvent-switchable procedure was used for the preparation of such important drugs as Celebrex and SC-560 as well as their isomers in gram scale. The possible reaction mechanism is discussed.
An efficient route to 3-trifluoromethylpyrazole via cyclization/1,5-H shift and its applications in the synthesis of bioactive compounds
Wang, Yongdong,Han, Jing,Chen, Jie,Cao, Weiguo
, p. 8256 - 8262 (2015/10/05)
A methodology for regioselective synthesis of 3-trifluoromethylpyrazole from the reaction of trifluoromethyl alkenone and tosylhydrazone has been developed. The reaction was proposed to proceed through a tandem cyclization and 1,5-H shift reaction, which can be applied to the synthesis of bioactive compounds like Celecoxib, Mavacoxib, and SC-560.
Synthesis of 3-trifluoromethylpyrazoles via trifluoromethylation/ cyclization of α,β-alkynic hydrazones using a hypervalent iodine reagent
Ji, Guojing,Wang, Xi,Zhang, Songnan,Xu, Yan,Ye, Yuxuan,Li, Ming,Zhang, Yan,Wang, Jianbo
supporting information, p. 4361 - 4363 (2014/04/17)
A mild and efficient method for the synthesis of 3-trifluoromethylpyrazoles has been established via trifluoromethylation/cyclization of α,β-alkynic hydrazones using a hypervalent iodine reagent under transition-metal-free conditions.
New strategy for the regioselective synthesis of 1-phenyl-3- trifluoromethyl-1H-pyrazoles
Zanatta, Nilo,Amaral, Simone S.,Dos Santos, Josiane M.,Da Silva, Andréia M.P.W.,Schneider, Juliana M.F.M.,Fernandes, Liana Da S.,Bonacorso, Helio G.,Martins, Marcos A.P.
, p. 4076 - 4079 (2013/07/25)
A regioselective synthesis of 3-trifluoromethyl-1-phenyl-1H-pyrazoles (1,3-isomers) as well as their 1,5-isomers (5-trifluoromethyl-1-phenyl-1H- pyrazoles), is described. The 1,3-isomers were obtained from the reaction of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones with arylhydrazones followed by deprotective hydrolysis while the 1,5-isomer was obtained by direct cyclocondensation of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones with phenylhydrazine. An unequivocal assignment of the 1,3- and 1,5-isomers of the pyrazole products is given.
Process for arylating or vinylating or alkynating a nucleophilic compound
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Page 26, (2008/06/13)
The present invention concerns a process for arylating or vinylating or alkynating a nucleophilic compound. More particularly, the invention concerns arylating nitrogen-containing organic derivatives. The arylating or vinylating or alkynating process of the invention consists of reacting a nucleophilic compound with a compound carrying a leaving group and is characterized in that the reaction is carried out in the presence of an effective quantity of a catalyst based on a metallic element M selected from groups (VIII), (Ib) and (IIb) of the periodic table and at least one ligand comprising at least one imine function and at least one supplemental nitrogen atom as the chelating atoms.
Design and synthesis of novel celecoxib analogues as selective cyclooxygenase-2 (COX-2) inhibitors: Replacement of the sulfonamide pharmacophore by a sulfonylazide bioisostere
Uddin, Md. Jashim,Rao, P.N. Praveen,Knaus, Edward E.
, p. 5273 - 5280 (2007/10/03)
A group of celecoxib analogues in which the para-SO2NH 2 substituent on the N1-phenyl ring was replaced by a para-sulfonylazido (SO2N3) 4, or a meta-SO 2N3 8, substituent were designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 inhibition studies showed that 4-[5-(4-methylphenyl)-3-trifluoromethyl-1H- pyrazol-1-yl]benzenesulfonyl azide (4) with a para-SO2N3 substituent was a selective COX-1 inhibitor. In contrast, 3-[5-(4-methylphenyl)- 3-trifluoromethylpyrazol-1-yl]benzenesulfonyl azide (8a) having a meta-SO 2N3 substituent (COX-1 IC50 >100 μM; COX-2 IC50=5.16 μM; COX-2 selectivity index >19.3) is a selective COX-2 inhibitor. A molecular modeling (docking) study showed that the SO2N3 group of 8a inserts deep inside the secondary pocket of the COX-2 binding site. The SO2N3 moiety of 8a can undergo a dual H-bonding interaction via one of its SO2 oxygen-atoms, and an electrostatic (ion-ion) interaction via the terminal azido (N3) nitrogen-atom, to the guanidino NH2 of Arg 513 in the secondary pocket of COX-2. These observations indicate that an appropriately positioned SO2N3 moiety is a novel alternative bioisostere to the traditional SO2NH2 and SO2Me pharmacophores present in selective COX-2 inhibitors, that are only capable of H-bonding interactions with the COX-2 isozyme, for use in drug design.
Synthesis of fluorinated heterocycles
Sloop, Joseph C.,Bumgardner, Carl L.,Loehle, W. David
, p. 135 - 147 (2007/10/03)
Selected 1,3-diketones having a trifluoromethyl group and/or a fluorine in the 2-position were condensed with aromatic hydrazines, hydroxylamine, urea, thiourea, guanidine, and substituted anilines producing pyrazoles, isoxazoles, pyrimidines, and quinolines, respectively, in yields ranging from 27 to 87%.
