Catalytic Action of Azolium Salts. II. Aroylation of 4-Chloroquinazolines with Aromatic Aldehydes Catalyzed by 1,3-Dimethylbenzimidazolium Iodide.

Miyashita, Akira; Matsuda, Hideaki; Iijima, Chihoko; Higashino, Takeo

doi:10.1248/cpb.40.43

Cited by 23 publications

(8 citation statements)

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“…Initially 2,4,6-trichloropyrimidine was reacted with o , o -difluorobenzaldehyde and sodium hydride using N,N′ -dimethylbenzimidazolium iodide as a catalyst (Scheme 1). 30,31 Two dichloropyrimidine regioisomers were isolated for each aldehyde with the carbonyl group either in the primarily desired position 4 (compounds 1 , 2 ) or in position 2 ( 3, 4 ). The next step in the synthetic sequence was nucleophilic substitution of one chlorine atom by ammonia.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and anti-human immunodeficiency virus activity of substituted (o,o-difluorophenyl)-linked-pyrimidines as potent non‐nucleoside reverse transcriptase inhibitors

Čechová

Dejmek

Baszczyňski

et al. 2019

Antivir Chem Chemother

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With the worldwide number of human immunodeficiency virus positive patients stagnant and the increasing emergence of viral strains resistant to current treatment, the development of novel anti-human immunodeficiency virus drug candidates is a perpetual quest of medicinal chemists. Herein, we report a novel group of diarylpyrimidines, non-nucleoside reverse transcriptase inhibitors, which represents an important class of current anti-human immunodeficiency virus therapy. Series of diarylpyrimidines containing o,o-difluorophenyl (A-arm), 4-cyanophenylamino (B-arm), and a small substituent (e.g. NH2, OMe) at positions 2, 4, and 6 of the pyrimidine ring were prepared. The A-arm was modified in the para position (F or OMe) and linked to the central pyrimidine core with a variable spacer (CO, O, NH). Antiviral activities of 20 compounds were measured against wild type human immunodeficiency virus-1 and mutant reverse transcriptase strains (K103N, Y181C) using a cytoprotection assay. To the most promising structural motives belong the o,o-difluoro-p-methoxy A-arm in position 4, and the amino group in position 6 of pyrimidine. Single digit nanomolar activities with no significant toxicity (CC50 > 17,000 nM) were found for compounds 35 (EC50 = 2 nM), 37 (EC50 = 3 nM), and 13 (EC50 = 4 nM) having O, NH, and CO linkers, respectively.

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Section: Resultsmentioning

confidence: 99%

Synthesis and anti-human immunodeficiency virus activity of substituted (o,o-difluorophenyl)-linked-pyrimidines as potent non‐nucleoside reverse transcriptase inhibitors

Čechová

Dejmek

Baszczyňski

et al. 2019

Antivir Chem Chemother

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“…To this end, 4-phenyl-substituted derivatives were chosen as substrates to prevent any undesired reactions with the carbon at position 4 of the quinazoline core, which is highly susceptible to nucleophilic attack. Based on the successful examples described in previous reports, 19 the optimal reaction conditions were investigated. Thus, the reaction of chloride 1 in the presence of dimethylimidazolium iodide 4 (10 mol%, NHC precursor) and NaH (base) in DMF at room temperature for 4 h, afforded the desired ketone 9, albeit with a low yield (entry 1).…”

Section: Resultsmentioning

confidence: 99%

“…18 Previously, we reported on the use of the NHC-catalyzed aroylation of Cl-and sulfonyl substituted N-heteroarenes, 19 arylimidoyl chlorides, 20 and electron-deficient 4-fluorobenzenes 21 to afford keto derivatives, demonstrating the applicability of this transformation to a variety of N-heteroarenes. However, in these examples, the heteroarene substitution positions were limited to the carbons of those imine moieties bearing a leaving group, with any substitution at those carbon atoms not adjacent to the nitrogen atoms being unknown.…”

Section: Introductionmentioning

confidence: 98%

Nucleophilic Aroylation on Fluoroquinazolines Catalyzed by N-Heterocyclic Carbenes

Suzuki¹,

Tachikawa²,

Nakagawa³

2018

HETEROCYCLES

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-We report on the synthesis of 7-benzoyl-and 7-heteroaroylquinazolines from 7-fluoroquinazolines and aromatic aldehydes by N-heterocyclic carbene (NHC)-catalyzed nucleophilic aromatic substitution, showing that the NHC derived from 1,3-dimethylimidazolium iodide outperformed those originating from other azolium (e.g., thiazolium and triazolium) salts. Additionally, the developed methodology allowed the preparation of 5-and 8-aroylquinazolines from the corresponding fluoroquinazolines.

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“…Azolium 5 catalyzed syntheses of heteroaromatic ketones 10 and ketimines 12 (and subsequently 1,2-diketones 13) by the reaction of aldehydes 1 with heteroaryl halides 9 19 and imidoyl chlorides 11, 20 respectively, have also been reported. …”

Section: Methodsmentioning

confidence: 97%

Acyl anion synthons: benzotriazole stabilized compared to classical

Katritzky¹,

Kirichenko²

2006

Arkivoc

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Catalytic Action of Azolium Salts. II. Aroylation of 4-Chloroquinazolines with Aromatic Aldehydes Catalyzed by 1,3-Dimethylbenzimidazolium Iodide.

Cited by 23 publications

References 0 publications

Synthesis and anti-human immunodeficiency virus activity of substituted (o,o-difluorophenyl)-linked-pyrimidines as potent non‐nucleoside reverse transcriptase inhibitors

Synthesis and anti-human immunodeficiency virus activity of substituted (o,o-difluorophenyl)-linked-pyrimidines as potent non‐nucleoside reverse transcriptase inhibitors

Nucleophilic Aroylation on Fluoroquinazolines Catalyzed by N-Heterocyclic Carbenes

Acyl anion synthons: benzotriazole stabilized compared to classical

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