‘One-pot’ synthesis of 4-substituted 1,5-diaryl-1H-pyrazole-3-carboxylates via lithium tert-butoxide-mediated sterically hindered Claisen condensation and Knorr reaction

Jiang, Jianan; Huang, Wanzhi; Zhai, Jiao-Jiao; Liu, Hongwei; Cai, Qi; Xu, Liuxin; Wang, Wei; Ji, Yafei

doi:10.1016/j.tet.2012.11.012

Cited by 27 publications

(18 citation statements)

References 86 publications

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“…The diketoesters 88 was converted into the desired 1,5-isomers 90 in the yields of 60–66%. Meanwhile, N -arylhydrazones 91 were obtained in the yields of 24–31% ( Scheme 28 ) [ 36 ].…”

Section: The Main Methods Of Access To the Pyrazole Nucleusmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

et al. 2018

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Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.

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“…The diketoesters 88 was converted into the desired 1,5-isomers 90 in the yields of 60–66%. Meanwhile, N -arylhydrazones 91 were obtained in the yields of 24–31% ( Scheme 28 ) [ 36 ].…”

Section: The Main Methods Of Access To the Pyrazole Nucleusmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

et al. 2018

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“…Unless otherwise indicated, all reagents were obtained from commercial sources and used as received without further purification. 4‐Aryl‐2,4‐diketoesters 2 were freshly prepared from alkylphenones and diethyl oxalate . All reactions were carried out in oven‐dried glassware and monitored by thin layer chromatography (precoated silica gel plates containing HF 254 ).…”

Section: Methodsmentioning

confidence: 99%

“…Continuing our recent work involving the synthesis of highly substituted 1 H ‐pyrazole‐3‐carboxylates , herein, we reported a viable one‐pot approach to highly substituted 1 H ‐pyrazole‐5‐carboxylates from easily available 4‐aryl‐2,4‐diketoesters and arylhydrazine hydrochlorides. In the methodology, more active 2‐carbonyl group of 4‐aryl‐2,4‐diketoesters was first blocked with methoxyamine hydrochloride to give the 2‐methoxy imine derivatives, and a compelling in situ attack of arylhydrazines on the 4‐carbonyl group, followed by a cyclization with the elimination of methoxylamine led to the desired 1 H ‐pyrazole‐5‐carboxylates.…”

Section: Introductionmentioning

confidence: 91%

One‐Pot Synthesis of Highly Substituted 1H‐Pyrazole‐5‐carboxylates from 4‐Aryl‐2,4‐diketoesters and Arylhydrazines

Zhai

Guo

et al. 2015

Journal of Heterocyclic Chem

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A one‐pot synthesis of highly substituted 1H‐pyrazole‐5‐carboxylates 1 has been developed starting from easily available 4‐aryl‐2,4‐diketoesters 2 and arylhydrazine hydrochlorides 3. More active 2‐carbonyl group of 2 was blocked with methoxyamine hydrochloride to give 2‐methoxy imine intermediates, which were then subjected to condensation cyclization with 3 in situ to provide the desired products 1. In addition, the geometrical configuration of 1aa was unambiguously confirmed by single crystal X‐ray crystallography.

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“…Two specific hydrazines ( 44a,b ) were easily prepared via an in situ one-pot diazotation/reduction step from suited aniline ( 43a,b ) …”

Section: Chemistrymentioning

confidence: 99%

“…Two specific hydrazines (44a,b) were easily prepared via an in situ one-pot diazotation/reduction step from suited aniline (43a,b). 47 The synthesis of N 5 -methyl amide 12 was accomplished in 16% overall yield after a four-step protocol by means of an Nalkylation of γ-carboline 45q, as a key synthetic modification (Scheme 2).…”

Section: ■ Chemistrymentioning

confidence: 99%

Identification, Structure–Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators

et al. 2020

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Cystic fibrosis (CF) is a life-threatening autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR modulators have been reported to address the basic defects associated with CF-causing mutations, partially restoring the CFTR function in terms of protein processing and/or channel gating. Small-molecule compounds, called potentiators, are known to ameliorate the gating defect. In this study, we describe the identification of the 2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole core as a novel chemotype of potentiators. In-depth structure−activity relationship studies led to the discovery of enantiomerically pure 39 endowed with a good efficacy in rescuing the gating defect of F508del-and G551D-CFTR and a promising in vitro druglike profile. The in vivo characterization of γ-carboline 39 showed considerable exposure levels and good oral bioavailability, with detectable distribution to the lungs after oral administration to rats. Overall, these findings may represent an encouraging starting point to further expand this chemical class, adding a new chemotype to the existing classes of CFTR potentiators.

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‘One-pot’ synthesis of 4-substituted 1,5-diaryl-1H-pyrazole-3-carboxylates via lithium tert-butoxide-mediated sterically hindered Claisen condensation and Knorr reaction

Cited by 27 publications

References 86 publications

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

One‐Pot Synthesis of Highly Substituted 1H‐Pyrazole‐5‐carboxylates from 4‐Aryl‐2,4‐diketoesters and Arylhydrazines

Identification, Structure–Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators

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