Convenient entry to N-pyridinylureas with pharmaceutically privileged oxadiazole substituents via the acid-catalyzed C H activation of N-oxides

Geyl, Kirill K.; Baykov, Sergey V.; Tarasenko, M. V.; Зеленков, Лев Е.; Matveevskaya, Vladislava V.; Boyarskiy, Vadim P.

doi:10.1016/j.tetlet.2019.151108

Cited by 22 publications

(16 citation statements)

References 51 publications

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“…This method was later applied to the synthesis of pharmaceutically privileged oxadiazole-substituted urea, 102 (Scheme 28). [50] All the synthesized targets had cLogP values of < 3, which complies with the "lead-like" criteria.…”

Section: N-acylated 2-aminopyridines and 2-aminoquinolinessupporting

confidence: 56%

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

et al. 2020

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While remarkable progress has recently been made for the direct C−H‐functionalization of azines, its application is still limited by a lack of accessible functional groups (primarily carbon‐based) and poor regioselectivity. In contrast, C2‐functionalized pyridines and quinolines can be easily synthesized by treating readily available N‐oxides with various reagents under appropriate activation conditions. This review seeks to comprehensively document the available synthetic methods for introducing functional groups at the C2 position of pyridines and quinolines. In this work, we highlight recent developments in the C2‐functionalization of pyridine and quinoline N‐oxides and address both the mechanisms and regioselectivity of the reactions. We also describe the pathways and reactive species involved in these processes and highlight a number of medically relevant nitrogen heteroaromatics.

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Section: N-acylated 2-aminopyridines and 2-aminoquinolinessupporting

confidence: 56%

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

et al. 2020

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“…N -Oxides were synthesized according to literature procedures [ 51 ]. All other reactants and solvents were obtained from commercial sources.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The preparation and characterization of compounds 1a , 2a , and 2b were described by us previously [ 51 ]. Other oxadiazoles ( 1b , 3a , and 3b ) were synthesized via the acid-catalyzed reaction of corresponding pyridine- N -oxides with dialkylcyanamides according to the described protocol [ 51 ]. A mixture of the substituted pyridine- N -oxide (1 mmol), the dialkylcyanamide (2.0 mmol) and acetonitrile (1 mL, 10.0 mmol) was stirred at room temperature for 2 min, and then MsOH (144 mg, 1.5 mmol) was added dropwise within 3 min.…”

Section: Methodsmentioning

confidence: 99%

“…In this work, we aimed to achieve a better understanding of the nature of the stacking interactions involving oxadiazole moieties and their possible effects on both molecular and protein binding. Recently, we have already described the synthesis of N -pyridyl ureas bearing oxadiazole moiety [ 51 ]. Using the suggested synthetic strategy, we obtained and crystalized the representative set of 6 1,2,4-( 1 – 3a ), and 1,3,4-oxadiazole ( 1 – 3b ) based N -pyridyl ureas ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

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π–π Noncovalent Interaction Involving 1,2,4- and 1,3,4-Oxadiazole Systems: The Combined Experimental, Theoretical, and Database Study

et al. 2021

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A series of N-pyridyl ureas bearing 1,2,4- (1a, 2a, and 3a) and 1,3,4-oxadiazole moiety (1b, 2b, 3b) was prepared and characterized by HRMS, 1H and 13C NMR spectroscopy, as well as X-ray diffraction. The inspection of the crystal structures of (1–3)a,b and the Hirshfeld surface analysis made possible the recognition of the (oxadiazole)···(pyridine) and (oxadiazole)···(oxadiazole) interactions. The presence of these interactions was confirmed theoretically by DFT calculations, including NCI analysis for experimentally determined crystal structures as well as QTAIM analysis for optimized equilibrium structures. The preformed database survey allowed the verification of additional examples of relevant (oxadiazole)···π interactions both in Cambridge Structural Database and in Protein Data Bank, including the cocrystal of commercial anti-HIV drug Raltegravir.

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“Urea to Urea” Approach: Access to Unsymmetrical Ureas Bearing Pyridyl Substituents

et al. 2022

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A protocol for the synthesis of unsymmetrical ureas substituted by pyridyl/quinolinyl moiety has been developed. This method concluded in metal‐ and base‐free reamination of N,N‐dimethyl‐N‘‐hetaryl ureas with a wide range of aryl and alkyl amines. The isolated yields vary from 40 to 96% depending on the nucleophilicity of the amines. The scope of this method includes more than 50 examples. The reaction is not hindered by either donor or acceptor groups as well as diverse functionalities. The synthesis can be easily scaled to gram quantities. Theoretical calculations supported by experimental data allowed us to propose a plausible mechanism for the process. This reaction takes place through the intermediate formation of hetaryl isocyanate.

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Convenient entry to N-pyridinylureas with pharmaceutically privileged oxadiazole substituents via the acid-catalyzed C H activation of N-oxides

Cited by 22 publications

References 51 publications

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

π–π Noncovalent Interaction Involving 1,2,4- and 1,3,4-Oxadiazole Systems: The Combined Experimental, Theoretical, and Database Study

“Urea to Urea” Approach: Access to Unsymmetrical Ureas Bearing Pyridyl Substituents

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