HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• Luan A. Martinho Carlos Kleber Z. Andrade Instituto de Química, Laboratório de Química Metodológica e Orgânica Sintética (LaQMOS), Universidade de Brasília, 70904-970, Brasília, DF, Brazil 10.3762/bjoc.20.55 Abstract The imidazo[1,2-a]pyridine moiety is present in drugs with several biological

• existing ones. Keywords: GBB-3CR; imidazo[1,2-a]pyridine; microwave; phosphotungstic acid; Introduction Imidazo[1,2-a]pyridine is a privileged structure that plays an important role in organic synthesis and in the pharmaceutical industry. This scaffold is present in drugs with several biological

• (insomnia). Some recent synthetic approaches to imidazo[1,2-a]pyridine scaffolds include synthetic pathways of transition metal-catalyzed reactions [14], cyclization [15], condensation [16], heteroannular [17], and photocatalytic reactions [18]. These approaches usually involve non-trivial reaction

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• , Zaporizhzhya National University, Zhukovsky str., 66, Zaporizhzhya, 69600, Ukraine 10.3762/bjoc.19.53 Abstract Peptidomimetics with a substituted imidazo[1,2-a]pyridine fragment were synthesized by a tandem of Groebke–Blackburn–Bienaymé and Ugi reactions. The target products contain substituted imidazo[1,2-a

• –Bienaymé reaction; imidazo[1,2-a]pyridine; isocyanide; multicomponent reaction; peptidomimetic; Ugi reaction; Introduction The use of isocyanide multicomponent reactions (IMCR) to prepare biologically active compounds is one of the most promising tools in modern organic and medicinal chemistry. Therefore

• structures containing a substituted imidazo[1,2-a]pyridine fragment, such as anticancer [5], antibacterial [6], antifungal [7], antiviral [8], anti-inflammatory [9], antimalarial [10], antiparkinsonian [11] and antituberculous activities [12]. In addition, some derivatives show enzyme inhibition [13] and can

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• ,t and 4x,y). Lastly, we explored a few heterocycles that resemble imidazo[1,2-a]pyridine to vindicate the generality of this method. Gratifyingly, 6-phenylimidazo[2,1-b]thiazole, 2-phenylbenzo[d]imidazo[2,1-b]thiazole, and 2-phenylimidazo[1,2-a]pyrimidine participated well under the standard

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

• groups in many biologically active substances and pharmaceuticals, such as zolpidem, alpidem, and GSK812397 [1][2][3]. Therefore, the development of multiple chemical modification methods, at the 3-position of the imidazo[1,2-a]pyridine skeleton, for the synthesis of 3-substituted-imidazo[1,2-a]pyridines

• with an imidazo[1,2-a]pyridine ring, this study focused on the Cu-catalyzed one-pot C(sp2)–Se and C(sp)–Se bond formation for the synthesis of novel alkynyl imidazopyridinyl selenides using Se powder, 2-arylimidazo[1,2-a]pyridines, and terminal alkynes. Results and Discussion Synthesis of alkynyl

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• yields the desired products 127 (Scheme 50). 8.2 Fused pyridines Fused pyridines have been profoundly known for various pharmacological activities. Moreover, the imidazo[1,2-a]pyridine core is found in various drugs like zolpidem (128), alpidem (129), olprinone (130). They are also promising antiviral

• , antiulcer, anxiolytic, antiherpes agents [115][116][117][118][119]. Similarly, pyrazolo-pyridines are found to be potent antibacterial (131), cytotoxic (132), antiproliferative (133) and antimalarial (134) agents (Figure 10) [120][121]. 8.2.1 Imidazo[1,2-a]pyridine: Sun and co-workers [122] accomplished the

• between benzimidazole-linked aminopyridine and Lewis acid activated aldehyde which further on nucleophilic addition with substituted isocyanide leads to intermediate B. A 5-exo-dig intramolecular cyclization with isocyanide aids in the formation of the imidazo[1,2-a]pyridine intermediate C. The final

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• some reported to act as antioxidants and show activities that are medicinally relevant; hence, the development of efficient methods for their synthesis is an important objective. Herein, a simple method for the synthesis of selenides and diselenides bearing imidazo[1,2-a]pyridine rings and their

• anticancer activity are described. The double C–H selenation of imidazo[1,2-a]pyridine with Se powder was catalyzed by CuI (10 mol %) ligated with 1,10-phenanthroline (10 mol %) at 130 °C under aerobic conditions. The selenides or diselenides were prepared almost selectively using selenium powder in an

• appropriate quantity under otherwise identical reaction conditions. The prepared selenides and diselenides bearing two imidazo[1,2-a]pyridine rings were all novel compounds. Among the prepared diselenides and selenides that exhibited cytotoxicity against cancer cells, bis[2-(4-methoxyphenyl)imidazo[1,2-a

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• ]pyridine ring has been synthesized via the microwave-assisted Mizoroki–Heck reaction. The efficient modification of the imidazo[1,2-a]pyridine ring has been achieved as late-stage functionalization, enabling and accelerating the generation of a library of compounds from a common precursor. Keywords: α

• -phosphonoacrylates; α-phosphonopropionates; imidazo[1,2-a]pyridine; microwave-assisted reaction; Mizoroki–Heck reaction; Introduction In the last few decades, the Mizoroki–Heck reaction has become one of the main tools in organic synthesis. Its use for the functionalization of a wide range of compounds cannot be

• of compounds from a common precursor and enables efficient generation of new chemical entities. Imidazo[1,2-a]pyridine constitutes an appealing scaffold in medicinal chemistry. It is present in a number of compounds, which exhibit many interesting biological properties. Its privileged character is

Aggregation-induced emission effect on turn-off fluorescent switching of a photochromic diarylethene

• Luna Kono,
• Yuma Nakagawa,
• Ayako Fujimoto,
• Ryo Nishimura,
• Yohei Hattori,
• Toshiki Mutai,
• Nobuhiro Yasuda,
• Kenichi Koizumi,
• Satoshi Yokojima,
• Shinichiro Nakamura and
• Kingo Uchida

Beilstein J. Org. Chem. 2019, 15, 2204–2212, doi:10.3762/bjoc.15.217

• imidazo[1,2-a]pyridine derivative, in which remarkable fluorescence was observed and no overlapping from the absorption band due to the large Stokes shift of the fluorescence [19][20]. Photochromic diarylethene systems with ESIPT moieties are already reported in some research groups [21][22][23]. Herein

• , we prepared a diarylethene incorporating the imidazo[1,2-a]pyridine moiety with ESIPT ability and reported the fluorescence switching of the system. Results and Discussion The diarylethene 1o having an ESIPT moiety was prepared by a coupling reaction of asymmetric diarylethene 3 [24] and 6-bromo-2-(2

• ’-methoxyphenyl)imidazo[1,2-a]pyridine 4 [25] followed by ether cleavage according to Figure 1. The photochromic reaction and spectral changes are shown in Figure 2 and Figure 3. The photochromic absorption spectral changes in THF are shown in Figure 3. Upon UV light irradiation of the solution of 1o, the color

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• Figure S2 in Supporting Information File 1). Cs2CO3-mediated C(Het)–S bond formations of a heteroazole such as imidazo[1,2-a]pyridine, oxadiazole, and benzimidazole with diaryl disulfides without a transition metal catalyst have previously been developed [18][19]. The key step in these reactions is

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• greener oxidants [33]. During the writing of this review, we came across some reviews on IPs, however, their coverage is limited to the imidazo[1,2-a]pyridine nucleus deriving from either a particular starting material or to one type of reaction procedure (particularly C–H activation) with literature up

• [105][106]. Inspired from the history of IP synthesis Tajbakhsh et al. have utilized the biimidazole Cu(I) complex supported on magnetic Fe3O4 (MNP@BiimCu) as a heterogenous catalyst for the synthesis of imidazo[1,2-a]pyridine in an aqueous medium (Scheme 9) [107]. By their approach, they have avoided

• of biologically active imidazo[1,2-a] pyridine derivatives [108]. Encouraged by the direct synthetic strategies for imidazo[1,2-a]pyridines (IPs), Donthiri et al. have reported an efficient Cu-catalyzed C–H functionalization of pyridines with vinyl azide derivatives [109]. Their use of vinyl azide

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

• 2-amino-4-arylimidazoles are more reactive substrates for these syntheses leading to the stable Michael-type adducts with aldehydes and Meldrum’s acid than the previously investigated indole and imidazo[1,2-a]pyridine. Moreover, as it has been shown that their further transformations may result in

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• proceeds through a domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction sequence. Keywords: 2-aminochromene; domino reaction; imidazo[1,2-a]pyridine; 2-iminochromene; Michael addition; multicomponent reaction; oxidation; pyridine amination; Introduction Domino reactions are well

• the redox potentials of three or more reactants at a time and employment of a sequential one-pot strategy may become one of the reasonable solutions. The vast biological activity of the compounds, bearing the imidazo[1,2-a]pyridine scaffold makes this heterocycle of great importance to the fields of

• interesting approaches towards the imidazo[1,2-a]pyridine core are being published nowadays [25][26][27][28][29][30], this molecular entity is still a pursued synthetic target and novel routes to diverse imidazopyridines are of value. Another privileged scaffold for drug discovery is 2-aminochromene, which

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• thiocyanate functional group, which is a precursor group to many sulfur-containing functional groups, as well as heterocycles such as thiazoles and isothiazoles. The imidazo[1,2-a]pyridine core is a particularly interesting drug-like structure, e.g., electron poor, polar, of low basicity, etc. The scope of

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• , due to these higher energies of activation for reactions with thiophene or pyrrole, larger amounts of selenophene oligomers were formed in the presence of these less reactive heteroarenes. Then, the reactivity of imidazo[1,2-a]pyridine, which contains a very reactive C–H bond at C3-position was

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

• compounds are frequently found in bioactive naturally occurring compounds, as well as in the synthetic pharmacopeia. Imidazo[1,2-a]pyridine is an important heterocyclic system present in many molecules featuring diverse biological activities, such as antiviral, antimicrobial, antitumor, anti-inflammatory

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• are several drugs containing the imidazo[1,2-a]pyridine moiety such as zolpidem (treatment of insomnia) and olprinone (cardiotonic drug) and a lot of compounds in biological testing and preclinical evaluation such as soraprazan (clinical antiulcer compound), necopidem (sedative effect), and saripidem

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• synthesis of the biologically intriguing imidazo[1,2-a]pyridine-fused isoquinoline systems from readily available starting materials was achieved through the Groebke–Blackburn–Bienaymé reaction followed by a gold-catalyzed cyclization strategy. The synthetic approach is characterized by mild reaction

• , an aldehyde and an isocyanide proceeds through the isocyanide-involving formal [4 + 1] cycloaddition [39] affording the biologically important imidazo[1,2-a]pyridine scaffold. Due to the atom and step economy, high efficiency and intriguing biological profiles of the products, the GBB reaction has

• synthesis of biologically interesting heterocycles [43][44][45][46][47], we were interested in a practical synthetic strategy towards imidazo[1,2-a]pyridine-fused isoquinoline systems. We believe that this type of polycyclic systems may have interesting biological profiles [48]. Herein, we report our recent

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

• Ananda Herath and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2017, 13, 239–246, doi:10.3762/bjoc.13.26

• single-step liquid–liquid microextraction unit to remove high boiling point polar solvents and impurities and provides the target compounds in high purity with excellent overall yields. Keywords: imidazo[1,2-a]pyridine; imidazo[1,2-a]pyridin-2-yl-1,2,4-oxadiazole; liquid–liquid extraction module

• developed methodology, our next goal was to incorporate a carboxylic acid synthesis step into the flow process. As noted above, we previously reported the continuous-flow synthesis of imidazo[1,2-a]pyridine-2-carboxylic acids in a single, uninterrupted process directly from readily available starting

• overcome this issue a third reactor was placed in a heated silicone oil bath and a flow system was assembled as shown in Table 3. The first reaction, the formation of imidazo[1,2-a]pyridine-2-carboxylic acid, was performed in a 1000 μL reactor (glass chip) at 100 °C. The acid exiting the first reactor was

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

• diverse and biologically relevant heterocycles, and thus have been extensively investigated by organic and medicinal chemists to explore lead compounds in drug discovery efforts [7][8][9][10]. The imidazo[1,2-a]pyridine scaffold is a pharmaceutically important drug template, and its derivatives display a

• and peptic ulcers, respectively) [22]. As such, the imidazo[1,2-a]pyridine structure represents an intriguing synthetic target, and its further functionalization is leading to polycyclic fused heterocycles that may have interesting biological profiles [23]. Impressively, the imidazo[1,2-a]pyridine

• involves a formal [4 + 1] cycloaddition of isocyanides [30] and imines, generated from the amidines and aldehydes, allowing straightforward access to diverse imidazo[1,2-x]azines [31][32][33]. In view of the significance of the GBB reaction and the imidazo[1,2-a]pyridine core structure, the further

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