Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• [3,4-b]pyridines, pyrazolo[1,5-a]pyrimidines and pyrazolo[1,5-a]pyrimidinones [12][13][14][15][16][17][18]. The majority of methods used in the generation of the pyrazolo[1,5-a]pyrimidinones employ a two-step process, which first requires the synthesis and isolation of the intermediate 5-aminopyrazoles

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• feature (hetero)aryl aromatic groups such as 9-deazapurines, pyrimidines, pyridines and phenyl groups connected by a C–C bond to a sugar (or sugar mimic) as shown in Figure 4 [30][45][46][47][50][54][55][56][57]. The change in the nature of the glycosidic bond is accompanied by i) increased hydrolytic

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

• extensively employed as useful synthons in designing and constructing a plethora of fused pyrazoloazines of potential synthetic and medicinal interest viz pyrazolo[3,4-b]pyridines 7 [18], pyrazolo[1,5-a]pyrimidines 8 [19], pyrazolo[3,4-d]pyrimidines 9 [20][21], pyrazolo[3,4-b]pyrazines 10 [22], pyrazolo[5,1-c

• spiropyrazolo[3,4-b]pyridines 63 and 64 starting from 5-aminopyrazole (R = H, R1 = Me, 16), isatin 54 and α-cyanoacetic ester 62 or 15 in aqueous-mediated reaction in presence of NaCl. Regioisomeric pyrazolo[1,5-a]pyrimidines 65 were not formed in any of the tried reaction conditions. An increase in the amount

• ). Synthesis of pyrazolo[1,5-a]pyrimidines Pyrazolo[1,5-a]pyrimidines, structural isomers of pyrazolo[3,4-b]pyridines, are of interest because they constitute an important class of heterocycles which display biological and pharmacological activities and are useful precursors in the synthesis of many

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• small modifications to nucleobases, such as the 8-vinyldeoxyadenosine [21], has led to the introduction of fluorescence. Considering the differences in the structures of purines and pyrimidines, adenine is unique amongst the natural bases as it offers several sites for modifications: C2, C8, the C6

• pyrimidines, only the C5 and C6 positions are available for modifications without directly perturbing the base-pairing properties. The subtle differences between the nucleobases within a class could lead one to believe that the chemistry developed for modifications of adenine would translate easily to guanine

• found to be general for a large set of 4-hydroxy-5-(o-aminoarylthio)pyrimidines [39]. The mechanism was thought to proceed via protonation of a pyrimidine ring nitrogen which activates it to nucleophilic attack by an unprotonated anilino nitrogen on the positive C4 of the pyrimidine ring which carries

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• metals found in Langlois’ reagent could be responsible for reaction initiation. The scope was evaluated on pyridines, pyrroles, indoles, pyrimidines, pyrazines, phthalazines, quinoxalines, deazapurine, thiadiazoles, uracils, xanthenes and pyrazolino-pyrimidines (Scheme 35). The combination of previous

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• derivatives, there is great interest in imidazo[1,5-annelated]diazines due to their diverse pharmacological actions and bioisosterism with imidazo[4,5-d]pyrimidines (purines). The presence of a bridgehead nitrogen atom is a common structural motif of these heterocyclic systems. For example, compounds with the

• imidazo[1,5-a]pyrazine structure show inhibitory activity against kinases BTK [1], MEK [2], ACK1 [3], mTORC1(2) [4], c-Src [5], growth factor IGF-1R [6] and act as the antagonists of Hedgehog pathway dependent malignancies [7]. Imidazo[1,5-a]pyrimidines are inhibitors of the bone morphogenic protein [8

• ], antitumor agents [9], and are stimulators of guanylate cyclase [10], whereas imidazo[1,5-c]pyrimidines demonstrate anti-infectious effects in the treatment of brucellosis [11], etc. However, the chemistry, medicinal chemistry and pharmacology of imidazo[1,5-b]pyridazines, with the imidazole ring connected

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

• -ones in acidic conditions occurs through the formation of the adamantyl cation. Keywords: adamantylation; azolo-1,2,4-triazines; J-coupling; 15N-labelled; NMR spectra; 1,2,4-triazolo[1,5-a]pyrimidines; Introduction The incorporation of an adamantyl moiety in bioactive molecules and analogues of

• this approach for the syntheses of 15N-labelled tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines [25] starting from 15N-labelled 5-aminotetrazole. However, due to proton tautomerism, the use of single-labelled [2-15N]-5-aminotetrazole led to the formation of isotopomer mixtures, which

• JHN interactions with the H2 proton in the 1,2,4-triazolo[5,1-c][1,2,4]triazines 19-15N2, 20-15N2, and 21a,b-15N2 and the H2 and H6 protons in the 1,2,4-triazolo[1,5-a]pyrimidines 23-15N2 and 24-15N2 permitted the straightforward assignments of the labelled 15N atoms (see Scheme 2 and Scheme 3). The

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• de Química de Heterociclos (NUQUIMHE), Department of Chemistry, Federal University of Santa Maria (UFSM), 97105-900, Santa Maria, RS, Brazil 10.3762/bjoc.13.237 Abstract An efficient synthesis methodology for a series of tetrazolo[1,5-a]pyrimidines substituted at the 5- and 7-positions from the

• CCl3, which leads to tetrazolo[1,5-a]pyrimidines in high regioselectivity with R at the 7-position of the heterocyclic ring; and (b) precursor compounds with R = aryl or methyl, which leads to a mixture of compounds, tetrazolo[1,5-a] pyrimidines (R in the 5-position of the ring) and 2-azidopyrimidines

• theory (DFT) for energetic and molecular orbital (MO) calculations. Keywords: 5-aminotetrazol; azide–tetrazole equilibrium; 2-azidopyrimidine; β-enaminones; tetrazolo[1,5-a]pyrimidine; trifluoromethylatedtetrazolo[1,5-a]pyrimidines; Introduction Tetrazolo[1,5-a]pyrimidines have attracted attention in

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• prepared in fair yields by the reaction of gem-difluoroenones with aminopyridines, -pyrimidines and -pyridazines. Condensed heterocycles of this type play an important role as key core structures of various bioactive compounds. Further, starting with a chloroimidazopyridazine derivative, Pd-catalyzed

• demonstrated also good anticancer properties [11][12], while imidazo[1,2-a]pyrimidines 2 are also known for their antituberculosis activity [13], and imidazopyridazine 3 acts as a sirtuin modulator [14]. On the other hand, the incorporation of fluorine or fluorinated groups into organic molecules has been

• [24]. Herein, we report the synthesis of imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazopyridazines with fluorinated side chains following an efficient strategy developed by Hajra et al. [25]. This methodology, developed for the synthesis of 3-aroylimidazopyridines, involves a copper

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• , benzimidazoles, pyrimidines, indoles, etc. [114][136][137][138][139]. Further improvements are in demand for the development of synthesis with solvent-less, time efficient, less byproducts, energy saving, easy handling procedures, etc. [112][140][141]. In 2016, Rousseau and co-workers reported a solvent-free

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• of imides with alkyl halogenides, and the results are presented in this paper. Until now, ball milling N-alkylations of ureas [15], hydrazones [16], imines [17][18], pyridines [19], pyrimidines [20], imidazoles [21], secondary amines [22], as well as allylic alkylation reactions [23] were reported in

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

• . Magnesium iodide-catalyzed synthesis of quinazolines. Ferrous chloride-catalyzed aerobic dehydrogenation of 1,2,3,4-tetrahydroquinolines. Cu(I)-catalyzed oxidative aromatization of indoles. Putative mechanism of the transformation. Oxidative dehydrogenation of pyrimidinones and pyrimidines. Putative

New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties

• Daria G. Selivanova,
• Alexei A. Gorbunov,
• Olga A. Mayorova,
• Alexander N. Vasyanin,
• Igor V. Lunegov,
• Elena V. Shklyaeva and
• Georgii G. Abashev

Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158

• scanning tunneling microscopy. Results and Discussion Synthetic toolbox The objective of the presented work involves the design and further synthesis of 4,6-diaryl-substituted 2-(pyrrol-1-yl)pyrimidines, embedding 9-[ω-(4-methoxyphenoxy)alkyl]carbazole moieties as substituents, one of which is directly

• ethanolic media resulted in the formation of 1,3-diarylsubstituted prop-2-en-1-ones 6a,b [23]. Cyclization of chalcones 6a,b with guanidine sulfate followed by oxidation with hydrogen peroxide gave rise to 2-amino-4,6-disubstituted pyrimidines 7a,b [24]. 2-(1H-Pyrrol-1-yl)pyrimidines 8a,b were synthesized

• 7a,b are collected in a Table placed in Supporting Information File 1. Further it has been established that solvatochromism is inherent not only to these newly synthesized chromophores 7a,b, but also to the whole set of 2-amino-4,6-diarylsubstituted pyrimidines even of the less complicated structure

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• , as these enzymes can be utilized in drug design and hence has value to the medical community as well. These enzymes also are generally regioselective for the position 9 of purines and the position 1 of pyrimidines which is a persisting challenge in the chemical synthesis of biologically active

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• living cells these pathways associate interconversions between purines and pyrimidines [34][35]. Furthermore, the nitrogen-rich intermediate 5-amino-6-(D-ribitylamino)uracil comprises building blocks that are commonly found under prebiotic conditions. Once phosphorylated (as discussed previously, via

• complementarity is the most obvious feature of processes of life is that of interactions involving nucleic acids. In these molecules, complementarity, which leads to the famous double helical structure, is a straightforward consequence of steric rules between isosteric piles of pairs of purines and pyrimidines

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• phosphoramidite chemistry. The alkyne groups as reactive precursors are attached to the oligonucleotide [13], especially at the 5-position of pyrimidines [13], the 7-position of 7-deazapurines [14], and the 2’-position of ribofuranosides [11][15]. These positions were chosen since they are typically accepted by

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• 2.4.2.4) phosphorylases [36], and (ii) the role of structural features and electronic properties of the pyrimidine bases and nucleosides in the recognition by E. coli nucleoside phosphorylases. Results and Discussion Thioxo- and 6-aza-pyrimidines used in the transglycosylation reaction with recombinant E

• differences of tautomeric structures of pyrimidines studied and their recognition by E. coli UP vs TP in the glycoside bond formation: Activation of uracil and thymine as well as their related analogues in the chemical synthesis of nucleosides consists in the trimethylsilylation giving rise to the formation

• catalytic site that are directly involved in the hydrogen bonding with pyrimidines and types of these interactions [3][52][53][54][55][56] (vide infra). Indeed, except for the side-chain Arg171/C-4 carbonyl interaction, several variants of direct hydrogen binding between the side-chains of Ser186 and Lys190

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• -metathesis of a challenging homoallylic urea substrate, which proceeds in good yields in the presence of an organic phosphoric acid. Keywords: cross-metathesis; natural products; pyrimidines; Tsuji–Trost reaction; synthetic methods; Introduction Chiral pyrimidine motifs constitute prevalent structural

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• or pyrimidines with subsequent aromatization of the heterocyclic ring. We also noticed that the final composition of these markers was dependent on the reaction conditions during the drug synthesis [24]. In order to unequivocally confirm the presence of newly identified markers in the reaction

• halogenated pyridines and pyrimidines. During our search for new "route markers" of amphetamine analogues synthesized by the Leuckart method, we focused our attention on two groups of heterocycles, that were preliminary identified by GC–MS analysis as 3,4,5-triaryl-2,6-dimethylpyridines P5 [32][33] and 3,5

• teams in the construction of polyarylated benzenes [56], pyridines [57][58][59][60], thiophenes [61][62], quinoxalines [63], pyrazoles [64] pyrroles [65], pyrimidines [66][67], benzofuranes [68], imidazo[1,2-a]pyridines [69], diaryl/heteroaryl methanes [70], and indoles [71], bearing differently

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• compound 49 was isolated (Scheme 19). It should be noted that in all cases, tetrasubstituted pyrimidines were involved in the RCM and the substituents in the α position of the N-heteroatoms might have a role in the success of these reactions by causing steric hindrance around the nitrogen and thus

• preventing the catalyst deactivation. In 2013, Moss generalized the method to the formation of azepines fused with a variety of heteroaromatics including pyrimidines, pyridines, thiazoles and pyrrazoles [59]. Interestingly, most of the heteroaryls possess a chlorine substituent but no explanation was given

• moieties such as pyridines, pyrimidines, imidazoles and pyrazoles (Scheme 37). From the selected examples discussed above, we tried to delineate some trends regarding to the use of alkenes possessing N-heteroaromatics in RCM and CM. In RCM, GI and GII are usually preferred and diluted conditions are

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

• Mingxing Liu,
• Jiarong Li,
• Hongxin Chai,
• Kai Zhang,
• Deli Yang,
• Qi Zhang and
• Daxin Shi

Beilstein J. Org. Chem. 2015, 11, 2125–2131, doi:10.3762/bjoc.11.229

• ]. For example, ibrutinib, sildenafil, allopurinol and zaleplon are famous pyrazolopyrimidine drugs. Because of the importance of pyrazolo[3,4-d]pyrimidines, many methods for the synthesis of pyrazolo[3,4-d]pyrimidines have been explored. Some examples include the condensation of 5-aminopyrazole-4

• ). But when benzaldehyde was switched to anisaldehyde, the expected product was not obtained and pyrazolo[3,4-d]pyrimidines was isolated (Scheme 1B). Inspired by this phenomenon, we conducted detailed studies and found a new convenient synthesis of pyrazolo[3,4-d]pyrimidines. To the best of our knowledge

• , this is a novel methodology for the synthesis of pyrazolo[3,4-d]pyrimidines by the reaction of hydrazines, methylenemalononitriles, aldehydes and alcohols. During the preparation of this manuscript, Liu et al. reported the synthesis of pyrazolo[3,4-d]pyrimidines from 5-aminopyrazole-4-carbonitrile [48

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

• Marcel Mirel Popa,
• Emilian Georgescu,
• Mino R. Caira,
• Florentina Georgescu,
• Constantin Draghici,
• Raluca Stan,
• Calin Deleanu and
• Florea Dumitrascu

Beilstein J. Org. Chem. 2015, 11, 1079–1088, doi:10.3762/bjoc.11.121

• Fundulea, Calarasi, Romania 10.3762/bjoc.11.121 Abstract The three possible structural isomers of 4-(pyridyl)pyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their

• of 4-(2-pyridyl)pyrimidine the steric hindrance directs the reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new indolizines were structurally characterized through NMR spectroscopy. The X-ray

• , 4 and 5 (Figure 1) were obtained [14][15]. Based on our previous experience [21][22][23][24][25] we investigated the synthesis and structural characterization of new pyrrolo[1,2-c]pyrimidines that are 3-substituted with a pyridine unit and new indolizines substituted in positions 6 or 7 with 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

• esters with aminoazoles either stops at the formation of open-chain 2-(azolylamino)methylidene-3-oxo esters [6] or leads directly to azolo[1,5-a]pyrimidines [7][8][9] depending on the structure of the starting reagents and reaction conditions. We have recently found that the cyclization of

• polyfluoroalkyl-containing 2-ethoxymethylidene-3-oxo esters with aminoazoles in contrast to non-fluorinated analogues results in the stable dihydroazolo[1,5-a]pyrimidines containing a gem-aminoalcohol fragment at the polyfluoroalkyl substituent [10][11]. The reactions of ethyl 2-ethoxymethylidene-3-oxo-3

• -(polyfluoroalkyl)propionates with 3-amino-5-hydroxypyrazole allowed to obtain not only dihydropyrazolo[1,5-a]pyrimidines but also pyrazolo[3,4-b]pyridines due to the peculiarities of the binucleophile used [12]. To the best of our knowledge, there is no published data about the interaction of 2-ethoxymethylidene-3

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• pyrimidines) and (b) hydrogen-bonding complementarity (hydrogen-bond acceptors, A, pair with hydrogen-bond donors, D). Rearranging donor and acceptor groups on the nucleobases, while not changing the geometry of the Watson–Crick pair, creates an artificially expanded genetic information system (AEGIS). AEGIS

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• -aminoazoles, including thiazole [13][14] and 1,3,4-thiadiazole [15][16] derivatives, or 2-aminoazine-based heterocycles, such as pyridines [17][18][19], pyrimidines [20][21][22][23][24] and pyrazines [25][26][27], have recently been utilized as Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR