Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• aminoazole fragments. In all earlier described experiments with participation of different α-aminoazoles as binucleophiles the reaction cascade readily accomplished by the formation of fused heterocyclic systems [25]. An analogous three-component reaction involving indole or imidazo[1,2-a]pyridine

• derivatives instead of 2-aminoimidazoles is referred in the literature as Yonemitsu reaction or Yonemitsu-like reaction [26][27][28][29][30][31]. The similar Michael-type adducts 6 were isolated [31] from the reaction of imidazo[1,2-a]pyridine with aldehydes and Meldrum’s acid in acetonitrile in the presence

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• with trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a tertiary amine as base a broad range of pyridine derivatives was accessible (Scheme 3). According to its discoverer, we named this reaction Flögel pyridine synthesis [21]. The reaction is very flexible with respect to the employed

• alkoxyallenes, nitriles and carboxylic acids and due to the two differently protected oxygen functions of the pyridin-4-ols these intermediates could be further substituted, e.g., through palladium-catalyzed reactions, to give highly substituted pyridine derivatives in a great variety. The scope and limitations

• are excellent precursors for the synthesis of specifically substituted heterocycles (Scheme 30). The intramolecular aldol-type condensations leading to a manifold of pyridine derivatives PY was already subject of a review article [23]. In this report, we demonstrate that the β-ketoenamides KE are also

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• obtained as a mixture of mono- and bis(pyridine) adducts. In terms of initiation efficiency, the pyridine-derivatives turned out to be more efficient than the corresponding phosphine-containing complexes. In the copolymerization of NBE (46) and COE (47), complexes 49–52 afforded the corresponding

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• . Carbocyclic or heterocyclic fused pyridine derivatives are an important class of compounds omnipresent in natural products and biologically relevant synthetic compounds [23][24][25][26][27]. For example, imiquimod is an immune response modifier used to treat warts on the skin and certain type of skin cancer

• received less attention. For instance, the multicomponent reactions of aldehydes, 3-(1H-indol-3-yl)-3-oxopropanenitriles and 5-aminopyrazol or naphthylamine afforded indole substituted fused pyridine derivatives [56]. 2-Indole substituted pyridine derivatives have also been prepared through AlCl3-induced C

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• -hydroxyaryl)pyridine derivatives bearing a carboxylate or a nitrile group suitably placed at C3 position of the aza-ring has been achieved in acceptable chemical yields with a broad functional group tolerance. This sequential C–C/C–N bond making process proceeds through a regioselective allylic alkylation/aza

• products [4], medicines [5], chelating agents in transition metal complexes [6][7], and material science [8][9]. Pyridine derivatives such as vitamins B6, B3 (niacin), and nicotinamide adenine dinucleotide (NAD) play a significant role in the metabolism process of living organisms. Consequently, many

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• pyridine derivatives was possible on treatment with KOt-Bu at −23 °C, presumably with formation of potassium triflinate [27]. In our case, pyridine was used as solvent and the reaction mixture was heated up to 70 °C. This could allow pyridine itself taking the double role of nucleophile and base, leading

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• synthesis of polyarylated systems. All obtained ortho-methoxy-substituted derivatives of pyridine 2 and 6–9 as well as ortho-chloro-substituted pyridine derivatives 13, 15–17 are chiral molecules and therefore a method for enantiomer discrimination was needed, especially in the case of the planned

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• ’-O-acetylthiomethyl-containing RNA, produces various 2’-O-alkyldithiomethyl (RSSM)-modified RNAs bearing lipophilic or polar groups through a thiol disulfide exchange reaction with alkyldisulfanyl-pyridine derivatives (Scheme 3). In a preliminary evaluation, the RSSM modifications were shown to

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• not only be attributed to the fairish PLQY and the efficient RISC process from T1 to S1 of CN-P1 emitter, but also owed to the reasonable high T1, good charge mobility, and well-matched PL spectrum of the mCP host with the CN-P1 absorption spectrum. Still based on pyridine derivatives, Pan et al

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• pyrazolo[3,4-b]pyridine nucleus 37 (Scheme 6). Aziz et al. [51] developed an acid-catalyzed synthesis of pyrazolo[3,4-b]pyridine derivatives 40 through the reaction of enaminone 38 with 5-aminopyrazole (R = Ph, 16) in acetic acid (Scheme 7). The proposed reaction mechanism involves the generation of new

• enaminone intermediate 39 which underwent condensation and cyclization within C-4 of 5-aminopyrazole and the carbonyl group of the enaminone to generate pyrazolo[3,4-b]pyridine derivatives 40. However, the formation of pyrazolo[1,5-a]pyrimidine 41, a structural isomer of 40 was obtained when 1-NH-5

• CaCO-2. Lin et al. [52] developed the synthesis of pyrazolo[3,4-b]pyridine derivatives 45 via aza-Diels–Alder reaction of pyrazolylimines 43 with maleimides 44 (Scheme 8). Pyrazolylimines 43 were in turn obtained from the reaction of 5-aminopyrazole 16 with diisopropylformamide dimethyl acetal (R

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• method tolerates the presence of pyridine derivatives, alcohols, esters, carboxylic acids, Boc-protected amines, boronic pinacol esters and was applied to the late-stage functionalization of complex molecules. In 2016, the first metal-free photoredox-catalyzed radical thiol–yne reaction was reported by

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• . The same issue was previously noted in the study of N-alkylated tetrazolo[1,5-a]pyridine derivatives [43]. Similar to the situation observed for the 13C nuclei, a comparison of the 15N chemical shifts in the starting heterocycles 13-15N2, 20-15N2, and 23-15N2 and their N-adamantylated derivatives 15a

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• calcium channel blockers that reduces the transmembrane calcium current upon binding, thereby relaxing the heart muscles [50]. Interestingly, 1,4-DHP drugs are metabolized in the liver by CYP-450 enzymes and undergo oxidative dehydrogenation to generate the corresponding pyridine derivatives [51]. To

• understand and model these biological pathways, oxidative aromatization of 1,4-DHP to their corresponding pyridine derivatives has acclaimed wide attention. A variety of oxidants such as urea nitrate, BrCCl3/hν, nitric acid, nitric oxide, N-methyl-N-nitroso-p-toluenesulfonamide, DDQ etc. has been used to

• heating, ultrasonication and solvent-free conditions alleviated the drawbacks to a major extent [56][57][58][59][60][61]. One such useful strategy include manganese dioxide (MnO2)-mediated oxidative aromatization of 1,4-DHP 45 to afford substituted pyridine derivatives 46 under microwave conditions

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• An efficient and operationally simple synthesis of 7-deuteropyrazolo[1,5-a]pyridine and 7-deutero-1,2,4-triazolo[1,5-a]pyridine derivatives using α-H/D exchange of 1-aminopyridinium cations in basic D2O followed by a 1,3-cycloaddition of acetylenes and nitriles is presented. A high regioselectivity

• years deuteration became also an efficient tool in drug design [6]. Pyrazolo[1,5-a]pyridine and 1,2,4-triazolo[1,5-a]pyridine scaffolds attracted significant attention to the medicinal chemistry community during the past decade. For example, pyrazolo[1,5-a]pyridine derivatives were used in the design of

• -1,2,4-triazolo[1,5-a]pyridine derivatives by H/D exchange of 1-aminopyridinium cations followed by the reaction with acetylenes and nitriles. Results and Discussion N-Aminopyridinium salts are easily available via direct N-amination of parent pyridines. Salt 1a was prepared by N-amination of pyridine

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• of the mono- and bisalkynyl-substituted 6H-1,2-oxazines was additionally demonstrated by Lewis-acid-mediated conversion into highly substituted pyridine derivatives [25] by cycloaddition of in situ generated azapyrylium intermediates [26] and alkynes. Inspired by these previously reported results, we

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• ]pyridine derivatives. Reaction conditions: 2 (1.35 mmol), 3 (1 mmol), 4 (1.35 mmol), HClO4 (1 mmol), n-BuOH (4 mL), reflux. Yields refer to isolated yields. 2b R1 = 4-Cl; 2c R1 = 4-Me, 2d R1 = 4-Br; 3b R2 = 5-OMe; 3c R2 = 5-Cl; 3d R2 = 5-Br; 3e R2 = 5,7-Me2; 3f R2 = 7-F; 3g R2 = 5-I; 4b R3 = cyclohexyl

• . Mechanistic rationale for the MCR [36]. MCR to polycyclic fused imidazo[1,2-a]pyridine derivatives. Synthesis of imidazo[1,2-a]pyridine derivatives in indicated conditions [36].a Supporting Information Supporting Information File 576: Experimental procedures, characterization and spectral data for

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• -phosphonates and 2-acyl-1,2-dihydroisoquinoline-1-phosphonates. Three-component reaction of pyridine derivatives with ethyl propiolate and dialkyl phosphonates. Three-component reactions for the phosphorylation of benzothiazole and isoquinoline. Three-component synthesis of diphenyl [2-(aminocarbonyl)- or [2

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• or O-nonaflation led to functionalized pyridine derivatives. Scheme 1 illustrates this sequence with the synthesis of two 2,2´-bipyridine derivatives 4a or 5b that were obtained by employing picolinic acid chloride for the N-acylations followed by O-methylation with methyl iodide or by O-nonaflation

• using nonafluorobutanesulfonyl fluoride (NfF) as sulfonylating reagent. In subsequent publications we could demonstrate that this method can be used to synthesize a variety of functionalized pyridine derivatives, 2,2´-bipyridines or terpyridines [2][3][4]. An alternative entry to the crucial β

• carboxylic acids [33][34][35][36][37][38][39][40]. These components form α-alkoxy-substituted β-ketoenamides as precursors of highly substituted pyridine derivatives. We therefore tried to independently prepare β-ketoenamides with this substitution pattern starting from simple 1,3-diketones such as 1a. An

A convergent, umpoled synthesis of 2-(1-amidoalkyl)pyridines

• Tarn C. Johnson and
• Stephen P. Marsden

Beilstein J. Org. Chem. 2016, 12, 1–4, doi:10.3762/bjoc.12.1

• . Although the regioselectivities are not exceptionally high, the ready chromatographic separation of the various isomers makes this a synthetically tractable approach to 4-substituted (1-amidoalkyl)pyridine derivatives. Conclusion In summary, we have demonstrated a new umpoled disconnection for the one-pot

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• ]. The synthesis of a small collection of imidazo[1,2-a]pyridine derivatives was realised through the application of different scavenger resins for in-line purification as well as a number of liquid handlers to orchestrate the library synthesis effort (Scheme 24). Using this semi-automated process a

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• . Thus, we have found an effective and simple reaction for the preparation of substituted pyrimidine and pyridine derivatives. The resulting compounds are important pharmacophores or may be used as a starting material for synthesis of other functionalized pyrimidines through nucleophilic substitution. X

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• reactions [19][20][21]. Recently, we and Perumal have demonstrated that the four-component reaction of arylamine, acetylenedicarboxylate, isatin and malononitrile can afford the spiro[indoline-3,4’-pyridine] derivatives in satisfactory yields [22][23][24]. We envisioned that functionalized spiro[indoline

• -3,4’-pyridine] derivatives can be synthesized by employing other nitrogen-containing nucleophiles such as hydrazine and imines in the similar four-component reactions. In fact, the four-component reaction of hydrazine, acetylenedicarboxylate, isatin and malononitrile for the formation of spiro

• four-component reaction for the efficient synthesis of the functionalized spiro[indoline-3,4’-pyridine] derivatives [23] a mixture of benzohydrazide and dimethyl acetylenedicarboxylate in ethanol was firstly stirred at room temperature for about fifteen minutes. Then isatin and malononitrile as well as

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• . Keywords: headspace analysis; natural products; polyketide biosynthesis; pyridine derivatives; streptazolin; volatile compounds; Introduction Actinomycetes are excellent producers of diverse and bioactive secondary metabolites. These metabolites belong to many different structural classes including

• . Natural products of bacteria containing a pyridine ring are rare. As an example, 1-(2-pyridinyl)ethanone was identified as a volatile of Enterobacter agglomerans [20]. Highly substituted pyridine derivatives can be found in bacterial thiopeptide antibiotics [21]. The streptopyridines of Streptomyces sp

• the production of other, usually less volatile secondary metabolites and whether different compounds can be detected by headspace analysis [7] compared to commonly used solvent extraction or adsorption/extraction procedures. Strain FORM5 has been reported to produce the tetrahydrocyclopenta[b]pyridine

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• 15 however, the cyclization was complete under these conditions furnishing bis(pyrimidine) derivative 25 as a single product in 60% yield. Although initially not desired the incomplete conversions of the bis(β-ketoenamides) leading to mono-pyridine derivatives such as 18b or to mono-pyrimidine