Regioselective Suzuki-Miyaura Reaction: Application to the Microwave-promoted Synthesis of 4,7-Diarylquinazolines

Kabri, Youssef; Verhaeghe, Pierre; Gellis, Armand; Vanelle, Patrice

doi:10.3390/molecules15052949

Cited by 20 publications

(11 citation statements)

References 37 publications

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“…In many instances, microwave heating has been shown to dramatically reduce processing times, increase product yields and to enhance product purities or material properties compared to conventionally processed experiments. [12][13][14][15][16][17] Although a variety of different microwave reactors and processing options are available today, 18 the overwhelming majority of all currently published microwave synthesis protocols describe the use of this non-classical heating principle in conjunction with sealed reactors. 12,13 Thus, substrate 1 was reacted with an excess of 2aminobenzothiazole in various reaction conditions, 3 including microwave-assisted and solvent-free ones, 6 in both sealed reactors and open flasks.…”

Section: Resultsmentioning

confidence: 99%

A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring

et al. 2014

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We report herein a new methodology for synthesizing quinazoline derivatives bearing an heteroarylamino moiety at position 4 of the quinazoline ring. As an alternative to the Buchwald-Hartwig cross-coupling reaction which appears, until now, as the only efficient way to react 4chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol% of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the SNAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2substitued-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest.

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Section: Resultsmentioning

confidence: 99%

A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring

et al. 2014

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“…We report herein the synthesis of such molecules from the reaction in water of 4-chloromethyl-2-methyl-5-nitro-1,3-thiazole ( 1 ) with various sulfinate anions under microwave irradiation. This is in continuation of our research program directed towards the study of electron transfer reactions in heterocyclic series [ 25 , 26 ] and microwave-assisted [ 27 , 28 ] eco-friendly processes [ 29 , 30 ]. The antiproliferative activity both of sulfones and of some α-dichlorinated sulfonyl derivatives was comparatively evaluated on the CHO and HepG2 cell lines, and results confirmed the promising antiproliferative effect of dihydrogenated sulfones towards the HepG2 cell line.…”

Section: Introductionmentioning

confidence: 82%

Synthesis and Promising in Vitro Antiproliferative Activity of Sulfones of a 5-Nitrothiazole Series

et al. 2012

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The synthesis in water of new sulfone derivatives under microwave irradiation is described. This eco-friendly process leads to the expected products in good yields by reaction of various substituted sulfinates (commercially available or obtained by reduction of the corresponding sulfonyl chlorides) with 4-chloromethyl-2-methyl-5-nitro-1,3-thiazole. In order to evaluate the antiproliferative effect of these compounds, several sulfone derivatives are also dichlorinated on the Cα next to the sulfonyl group. An evaluation on different cancer cell lines reveals promising selective in vitro antiproliferative activity toward HepG2 human cell lines by dihydrogenated sulfones, suggesting further research should be to explore their anticancer potential in the treatment of liver cancer.

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“…The first highly selective C‐4 Suzuki–Miyaura arylation of a 4,7‐dichloroquinazoline derivative was recently reported by Kabri et al 181. They investigated the reaction conditions providing site‐selectivity between the 4‐ and 7‐chlorinated positions of 4,7‐ dichloro‐2‐(2‐methyl‐1‐propenyl)‐6‐nitroquinazoline ( 489 ) and found that under the optimized conditions illustrated in Scheme the microwave‐promoted Pd(PPh 3 ) 4 ‐catalyzed reaction of this substrate with arylboronic acids led to the monosubstituted products 490 in 48–72% yields with complete site‐selectivity.…”

Section: Cross‐coupling Reactions Of Polyhalogenated Six‐membered Hmentioning

confidence: 99%

“…of arylboronic acids Ar 2 B(OH) 2 in a 9:1 mixture of DMF and EtOH at 150 °C for 3 h in the presence of 3.0 equiv. of Na 2 CO 3 181…”

Section: Cross‐coupling Reactions Of Polyhalogenated Six‐membered Hmentioning

confidence: 99%

Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

2012

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The palladium-catalyzed Suzuki-Miyaura reaction of multiply halogenated, electron-rich and electron-deficient heteroarenes is one of the most reliable and environmentally friendly tools for installing a wide range of non-functionalized and functionalized carbon substituents onto heteroaromatic systems with exquisite chemo-and site-selectivity. For substrates with different halogen groups the chemoselectivity of the Suzuki-Miyaura reactions has been found to be dependent on the reactivity difference between the halogens. However, the hardest achievement of selectivity in Suzuki-Miyaura monocouplings involving polyhalogenated heteroarenes with identical halogen atoms has been shown to be dominated by steric and electronic effects and the presence of directing groups at positions neighbouring the reaction sites. Moreover, in the case of symmetrically substituted dihaloheteroarenes with identical halogen atoms, highly selective monocoupling reactions have often been achieved only after a careful optimization of reaction parameters including the catalyst precursor, base, solvent, and the molar ratio between electrophile and organoboron reagent. This critical review with 341 references covers developments on the chemo-and site-selective Suzuki-Miyaura monocoupling reactions of polyhalogenated heteroarenes with different or identical halogen atoms. It also includes the synthesis of polysubstituted heteroarenes, not easily accessible by other means, via consecutive monocoupling reactions and/ or a more synthetically valuable approach involving one-pot polycoupling reactions.

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Regioselective Suzuki-Miyaura Reaction: Application to the Microwave-promoted Synthesis of 4,7-Diarylquinazolines

Abstract: New diarylquinazolines displaying pharmaceutical potential were synthesized in high yields from 4,7-dichloro-2-(2-methylprop-1-enyl)-6-nitroquinazoline by using microwave-promoted regioselective Suzuki-Miyaura cross-coupling reactions.

Cited by 20 publications

References 37 publications

A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring

A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring

Synthesis and Promising in Vitro Antiproliferative Activity of Sulfones of a 5-Nitrothiazole Series

Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

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