A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• (IMDA), and dehydrative re-aromatization reactions for the synthesis of imidazopyridine-fused isoquinolinones is developed. Gaussian computation analysis on the effect of the substitution groups for the IMDA reaction is performed to understand the reaction mechanism. Keywords: Groebke–Blackburn

• –Bienaymé (GBB); imidazopyridine; intramolecular Diels–Alder (IMDA); isoquinolinone; multicomponent reaction (MCR); re-aromatization; Introduction Multicomponent reactions (MCRs) have intrinsic green chemistry advantages of synthetic efficiency and operational simplicity. Performing post-condensational

• activities [9][10]. Imidazo[1,2-a]pyridine and isoquinolinone-kind scaffolds are privileged rings which can be found in drug molecules such as zolimidine [11], zolpidem [12], alpidem and antiemetic drug 5-HT3A antagonist palonosetron [13] (Figure 1). Imidazopyridine-fused isoquinolinones have been developed

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• protein in a manner comparable to the binding mode of known imidazopyridine inhibitors. Second, the possibility that reactants could covalently modify the enzyme was ruled out by analysis of the relevant literature. Finally, appropriate building blocks displaying additional functionalities capable of

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

• functionalization at the newly incorporated active methylene center. Cycle-1 is initiated with the reduction of bromomalonate 2a by the photoexcited catalyst PC* to malonyl radical I. This is followed by the Minisci-type addition of radical I to the imidazopyridine, preactivated by Lewis acidic Zn(OAc)2 [29]. PC

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• alcohol. We build on a commercially available imidazopyridine derivative and conceived a protecting group strategy to enhance solubility and selectivity to orchestrate the installation of the exocyclic amino and hydroxy groups. Results and Discussion 1-Deazaguanine Previously described syntheses for 1

• was carried out to obtain the desired 4-hydroxy-2,3,6-triaminopyridine (15) in unspecified yield (Scheme 3). This approach was optimized in 1975 by Schelling and Salemink using benzyl ether protection of the O4 during the imidazopyridine formation to increase the overall yield up to 37% [20]. The last

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• most likely factor, although other screenings for antimycobacterials reported the imidazopyridine derivative 26 as well as the ester 27 around the same time [160][161]. Concerning ester 27, it actually came from a DowAgroScience chemical library although, as early as 2004, the closely related compound

• cyclohexyl-bearing compound 34 [178] as well as the amidoethyl ether-bearing derivatives 35 and 36 [178][179][180]. Finally, a data base search on the sole amido-imidazopyridine component of this class of compounds came out with 1,500 derivatives which demonstrates that this ring system is still the focus of

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

• -alkynylselenides III exhibits a binding interaction between calf-thymus DNA and human serum albumin [13]. Moreover, imidazopyridine derivatives IV with selanyl groups, 3-aryl- or alkylselanylimidazo[1,2-a]pyridines, were reported to act as potential antioxidants and showed antiproliferative activity [14][15

• for the synthesis of unsymmetrical selenides with imidazopyridinyl groups substituted at position 3. Guo and Li et al. reported the reaction of Se powder with imidazopyridine and aryl iodides in the presence of KOH (2 equiv) as base using Cu(OAc)2 catalyst to form aryl imidazopyridinyl selenides [15

• powder with imidazopyridine and aryl iodides or alkyl halides in the presence of Na2CO3 (2 equiv) using the NiBr2/2,2-bipyridine system to give aryl or alkyl imidazopyridinyl selenides [24]. In these reactions, aryl iodides, arylboronic acids, and alkyl halides are coupled with Se powder to form diaryl

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

• ]pyridin-3-yl] diselenide showed an excellent anticancer activity and low cytotoxicity toward noncancer cells, suggesting that this diselenide is a potential lead compound for anticancer therapy. Keywords: anticancer activity; copper catalyst; diselenide; imidazopyridine; selenide; selenium; Introduction

• potential antioxidants and showed antiproliferative activity [27][28]. Consequently, they have attracted much attention, and methods for their syntheses have been actively pursued. A powerful method for the synthesis of 3-selanylimidazo[1,2-a]pyridines involves the C–H selenation using imidazopyridine and a

• successive use of imidazopyridine, Se powder, and aryl donors were developed in 2018 as more convenient methods for the synthesis of 3-selanylimidazopyridines. Guo, Li, et al. reacted imidazopyridines, Se powder, and arylboronic acids in the presence of Ag2CO3 (2 equiv) and Cs2CO3 (2 equiv) using a CuI/1,10

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

• ., anti-inflammatory, anticancer, antibacterial, anxioselective and antiprotozoal [3][4][5]. Furthermore, a number of drugs embracing the imidazopyridine (IP) skeleton have been commercially marketed with their trade names as minodronic acid (for the treatment of osteoporosis), olprinone (for acute heart

• encountered in the field of catalytic synthetic chemistry. The prime focus of this review is on the TM-catalyzed synthesis of differently fused IPs. In this review, a concise account on imidazopyridine (IP) syntheses has been documented for the benefit of the chemists working in the field. This will assist

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, People’s Republic of China 10.3762/bjoc.15.76 Abstract A diastereoselective approach to axially chiral imidazopyridine-containing biaryls has been developed. The reactions proceed through a radical cyclization cascade to construct

• been developed for the synthesis of chiral biaryls [3][4][5][6][7][8][9][10], reactions that take avantage of the central-to-axial chirality transfer have been less explored [11][12][13][14]. In addition, an antroposelective synthesis of imidazopyridine-based biaryls has not been reported. Nitrogen

• imidazopyridine-containing biaryls via central-to-axial chirality transfer (Scheme 1). Results and Discussion The substituents on the phenyl ring (R1) and at the propargylic position (R2) of carbamate 2 were varied to study their effects on the diastereoselectivity (Table 1). The electrolysis was conducted under

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

• may be found in crolibulin, an antitumor agent, undergoing phase II clinical trials [31], chromenotacrine CT-6, a potential anti-Alzheimer agent [32], and pranoprofen, a marketed anti-inflammatory drug [33]. Combination of chromene and imidazopyridine rings led to the discovery of compound A with

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

• , antiparasitic, hypnotic, etc. [1][2][3][4][5]. It is recognized as a key scaffold due to its broad occurrence in a number of drug candidates and drugs, such as zolpidem [6] (1a, used in the treatment of insomnia), and alpidem [6] (1b, an anxiolytic agent). Some imidazopyridine derivatives also act as β-amyloid

• DBU (1,8-diazabicycloundec-7-ene) under the same conditions as mentioned above, the desired imidazopyridine derivative 7a was isolated in 33% yield (Scheme 4). This one-pot process gives an overall yield very close to the two-step reaction (38%). Further, the halogen-substituted substrate 7e appeared

• heteroaromatic frameworks would be of much interest for biological studies in different areas of life sciences. Experimental Representative procedure for the synthesis of imidazopyridine 7a The syntheses of propargylic fluorides 5 and enones 6 were performed in a similar way as described before [26]. Synthesis

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• (9) and diphenyl-1,3,4-oxadiazole (10); and thioflavin-T analogues such as benzothiazole (11), benzoxazole (12), benzofuran (13), imidazopyridine (14), and benzimidazole (15); as well as quinoline (16) and naphthalene (17) derivatives (Figure 1B). In this review, we provide an overview of these AD

• reported for [125I]-labeled N,N-dimethylamino chalcones and aurones. Imidazopyridines The imidazopyridine core has also been used in developing novel Aβ imaging agents such as 140–142 (Scheme 10A). Initial SAR studies were based on derivatives 140a–j. One of the most successful imidazopyridines studied to

• appropriate pharmacokinetics for use in AD patients [93]. More in depth SAR studies of the imidazopyridine scaffold have been conducted by synthesizing the series of analogues 141a–w [94]. The effect of different substituents on binding affinity (Ki) for human Aβ plaques was examined (Table 12). In general

Extending the utility of [Pd(NHC)(cinnamyl)Cl] precatalysts: Direct arylation of heterocycles

• Anthony R. Martin,
• Anthony Chartoire,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2012, 8, 1637–1643, doi:10.3762/bjoc.8.187

• derivatives. To complete the study, experiments were performed at lower catalyst loading using imidazopyridine (13). This class of substrate has recently been involved, by Doucet et al. [45], in direct arylation with a catalytic charge of Pd(OAc)2 ranging from 0.1 to 0.01 mol %. In our case, comparable yields

• arylation of various benzothiophenes, thiophene and imidazopyridine. C–H functionalization of such heterocycles was performed in moderate to good yields by using only 0.1–0.01 mol % of precatalyst. This study highlights the fact that [Pd(NHC)(cin)Cl] complexes are multipurpose precatalysts as they may be

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• ]. In particular, they showed that the π-acceptor properties of NHC ligands such as 59 could be enhanced by introducing a second aromatic layer spanning the imidazopyridine-2-ylidene system, whereas the σ-donating abilities of both ligands remain basically equivalent. As a consequence, the new

• cyclophanic NHC ligand 60 and the related imidazopyridine-2-ylidene analog 59, generate gold complexes that behave in a divergent manner. While complex 59–AuCl, containing a poor π-acceptor ligand, is able to efficiently induce the (3 + 2) cycloaddition of eneallene 45 (R = Me, X = C(CO2Me)2, Ar = Ph, n = 1

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• a purity of >99.5% which is by far superior to the previously reported synthesis [65]. Finally, hydrolysis of the methyl ester provides telmisartan in an overall yield of about 50% compared to 21% as previously obtained (Scheme 44). Imidazopyridine Zolpidem (227) is a non-benzodiazepine hypnotic

• , and is part of the imidazopyridine class of pharmaceuticals. It is an agonist for the target receptor of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter. Zolpidem binds to GABA receptors at the same site as typical benzodiazepines. This drug is preferred to benzodiazepines for long term use