Solvent- and halide-free synthesis of pyridine-2-yl substituted ureas through facile C–H functionalization of pyridine N-oxides

Rassadin, Valentin A.; Zimin, Dmitry P.; Раскильдина, Г. З.; Ivanov, А. Yu.; Boyarskiy, Vadim P.; Злотский, С. С.; Kukushkin, Vadim Yu.

doi:10.1039/c6gc02556k

Cited by 41 publications

(17 citation statements)

References 84 publications

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“…All 2-pyridyl ureas ( U1–12 ) were synthesized via the acid-catalyzed reaction of corresponding N -oxides with dialkylcyanamides as described in our previous works ( Scheme 1 ) [ 33 , 34 , 37 ]. Briefly, the starting materials were mixed and heated in the presence of methanesulfonic acid (MsOH) in acetonitrile or under solvent-free conditions (depending of the reactivity and solubility of starting N -oxide).…”

Section: Resultsmentioning

confidence: 99%

“…The preparation and characterization of starting pyridine- N -oxides as well as U1–12 are described previously [ 33 , 34 , 37 ]. CuCl 2 , other reactants, and solvents were obtained from commercial sources.…”

Section: Methodsmentioning

confidence: 99%

“…This disappointing void is primarily related to the low synthetic availability of 2-pyridyl ureas and the need to utilize toxic reagents in their preparation process [ 27 , 28 , 29 , 30 , 31 ]. To address this latter problem, we recently came up with a simple protocol for the preparation of diverse N , N -dialkyl- N ′-(pyridin-2-yl)-ureas via acid-catalyzed reaction of pyridine- N -oxides with dialkylcyanamides [ 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Structure, and Antiproliferative Action of 2-Pyridyl Urea-Based Cu(II) Complexes

et al. 2022

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Relying on a recently suggested protocol that furnishes convenient access to variously substituted 2-pyridyl ureas, twelve hitherto unknown Cu(II) complexes have been synthesized in the present work and their structures were evaluated by elemental analysis, HRMS, IR spectroscopy, and X-ray diffraction study. Two structural motifs ([Cu(L)2Cl]+[Cl]− or (Cu(L)2Cl2) depending on the substitution pattern on the 2-pyridine fragment were revealed. In addition, antiproliferative action of the obtained compounds have been investigated against lung cancer cell lines (A549, NCI-H460, NCI-H1975), and healthy WI-26 VA4 cells were used to monitor non-specific cytotoxicity. Two nitro-group substituted complexes Cu(U3)2Cl2 (IC50 = 39.6 ± 4.5 μM) and Cu(U11)2Cl2 (IC50 = 33.4 ± 3.8 μM) demonstrate enhanced activity against the drug resistant NCI-H1975 cells with moderate selectivity toward normal WI-26 VA4 cells. The antiproliferative mechanism of cell death underlying the growth inhibitory effect of the synthesized complexes was studied via additional experiments, including the cell cycle analysis and the apoptosis induction test. Reassuringly, certain 2-pyridyl urea-based Cu(II) complexes exerted cell line-specific antiproliferative effect which renders them valuable starting points for further unveiling the anticancer potential of this class of coordination compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis, Structure, and Antiproliferative Action of 2-Pyridyl Urea-Based Cu(II) Complexes

et al. 2022

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“…Kukushkin and coworkers reported the synthesis of useful pyridine‐2‐yl substituted urea, 96 , via a 1,3‐dipolar cycloaddition pathway utilizing pyridine N ‐oxides 1 and dialkylcyanamides 95 under acidic and solvent‐free conditions (Scheme 27). [49] Notably, the C5‐functionalized product, 100 , predominated when the reaction was performed with 2‐methoxypyridine N ‐oxide. This method was later applied to the synthesis of pharmaceutically privileged oxadiazole‐substituted urea, 102 (Scheme 28).…”

Section: Simple C2‐h‐functionalizationmentioning

confidence: 99%

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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“…Compounds 1a 1 , 1b 2 , 1c 2 , 1d 3 , 1e 4 , 1f 2 , 1g 2 , 1h 4 , 1i 5 , 1j 6 , 1k 7 , 1l 8 , 1m 9 , 1o 10 are synthesized by the following procedure. 3-Chloroperoxybenzoic acid (15.0 mmol, 1.5 equiv) was added to a solution of N-heteroaromatic compound (10.0 mmol, 1.0 equiv) in CH2Cl2 (40 mL) at 0 °C .…”

Section: Synthesis Of Substratesmentioning

confidence: 99%

Electrochemical Deoxygenation of N-Heteroaromatic N-Oxides

Xu¹,

2019

Synlett

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An electrochemical method for the deoxygenation of N-heteroaromatic N-oxide to give the corresponding N-heteroaromatics has been developed. Several classes of N-heterocycles such as pyridine, quinoline, isoquinoline, and phenanthridine are tolerated. The electrochemical reactions proceed efficiently in aqueous solution without the need for transition-metal catalysts and waste-generating reducing reagents.

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Solvent- and halide-free synthesis of pyridine-2-yl substituted ureas through facile C–H functionalization of pyridine N-oxides

Abstract: A solvent- and halide-free atom-economical synthesis of practically useful pyridine-2-yl substituted ureas utilizes pyridine N-oxides and dialkylcyanamides.

Cited by 41 publications

References 84 publications

Synthesis, Structure, and Antiproliferative Action of 2-Pyridyl Urea-Based Cu(II) Complexes

Synthesis, Structure, and Antiproliferative Action of 2-Pyridyl Urea-Based Cu(II) Complexes

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

Electrochemical Deoxygenation of N-Heteroaromatic N-Oxides

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