A straightforward approach to N -substituted-2 H -indazol-2-amines through reductive cyclization

Schoene, Jens; Abed, Hassen Bel; Christmann, Mathias; Nazaré, Marc

doi:10.1016/j.tetlet.2017.03.031

Cited by 14 publications

(7 citation statements)

References 45 publications

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“…Balancing the required reactivity versus the desired reaction selectivity of the intermediate was considered crucial to avoid undesireds ider eactions, that is, nonproductive reduction of the nitro group, the aldehyde, or imine functionality.S urprisingly,p henylsilane,w hich is a well-established reagent for the reduction of tertiary phosphine oxides, [10, 12c, 13] was lesse fficient (55 %y ield;T able 1, entry 8), whereas triphenylsilane and methyldiethoxysilane led to the desired product in only at race amount or av ery low yield (Table1,e ntries 9a nd 10). To our surprise, easily separable and inexpensive 2,4,6, was comparably effective to diphenylsilane and af- Figure 1. a) Biologically active molecules with the 2H-indazole motif.b )2H-Indazole fluorophore.…”

Section: Resultsmentioning

confidence: 91%

A General One‐Pot Synthesis of 2H‐Indazoles Using an Organophosphorus–Silane System

Schoene

Abed

Schmieder

et al. 2018

Chemistry A European J

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A simple and direct approach for the regioselective construction of the privileged 2H-indazole scaffold is described. The developed one-pot strategy involves phospholene-mediated N-N bond formation to access 2H-indazoles. The amount of organophosphorus reagent was minimized by recycling the phospholene oxide with organosilane reductants. Starting from functionalized 2-nitrobenzaldehydes and primary amines, a mild reductive cyclization, involving the use of commercially available phospholene oxide and silanes, delivered a wide variety of substituted 2H-indazoles in good to excellent yields.

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Section: Resultsmentioning

confidence: 91%

A General One‐Pot Synthesis of 2H‐Indazoles Using an Organophosphorus–Silane System

Schoene

Abed

Schmieder

et al. 2018

Chemistry A European J

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“…The reaction showed good functional group tolerance and satisfactory yields could be obtained. Later, the same group [ 30 ] reported a one-pot, two-step approach to generate 2 H -indazol-2-amines 44 via a reductive cyclization of substituted hydrazones precursors 43 in the presence of organophosphorus reagent ( Scheme 14 b). In this process, substituted hydrazones 43 were easily prepared from 2-nitrobenzaldehyde 42 and phenylhydrazine.…”

Section: Synthesis Route For Indazole Derivativesmentioning

confidence: 99%

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

2018

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Indazole-containing derivatives represent one of the most important heterocycles in drug molecules. Diversely substituted indazole derivatives bear a variety of functional groups and display versatile biological activities; hence, they have gained considerable attention in the field of medicinal chemistry. This review aims to summarize the recent advances in various methods for the synthesis of indazole derivatives. The current developments in the biological activities of indazole-based compounds are also presented.

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“…While unsubstituted 1 H ‐indazoles and N1‐substituted‐1 H ‐indazoles are well represented in the chemical space and in particular populating the kinase ligand space, the 2 H ‐indazole framework is only rarely described. This is mainly attributed to the fact that until very recently, only a few direct methods allowed regioselective access to N2‐substituted 2 H ‐indazoles …”

Section: Resultsmentioning

confidence: 99%

Probing 2H‐Indazoles as Templates for SGK1, Tie2, and SRC Kinase Inhibitors

et al. 2019

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The broader and systematic application of a novel scaffold is often hampered by the unavailability of a short and reliable synthetic access. We investigated a new strategy for the design and synthesis of an array of N2‐substituted aza‐2H‐indazole derivatives as potential kinase inhibitors. Guided by a rational ligand alignment approach to qualify the so‐far underrepresented aza‐2H‐indazole scaffold, indazoles were connected at the N2 position with a phenyl spacer and an arylsulfonamide or amide linkage. Initial profiling against a panel of 30 kinases confirmed the in silico predicted selectivity bias. A synthesized focused library of 52 different aza‐2H‐indazole derivatives showed good initial selective inhibition against SGK1, Tie2, and SRC kinases, with the best representatives having IC50 values in the range of 500 nm. In a comparative computational study, these data were analyzed and rationalized in light of docking studies.

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A straightforward approach to N -substituted-2 H -indazol-2-amines through reductive cyclization

Cited by 14 publications

References 45 publications

A General One‐Pot Synthesis of 2H‐Indazoles Using an Organophosphorus–Silane System

A General One‐Pot Synthesis of 2H‐Indazoles Using an Organophosphorus–Silane System

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

Probing 2H‐Indazoles as Templates for SGK1, Tie2, and SRC Kinase Inhibitors

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