Syntheses of New Salts of Thieno[2′,3′;4,5]imidazo[1,2-a]pyridines Mesomeric 1-[2-amino-1-cyano-2-thio-]ethene-pyridinium ylides 1 are cyclizized to imidazo[1,2-a]pyridinium ylides 2 in the presence of HgO. S-alkylation of 2 leads to derivatives of 1-R1-2-thio-3-cyano-imidazo[1,2-a]pyridinium halides 3 or 4 . Alkylation products from 2 with α-haloketones are cyclizized to thieno[2′,3′ 4,5]imidazo[1,2-a]pyridinium salts 5 . 相似文献
A mild, catalytic, atom economical synthesis of imidazo[1,2‐a]pyridines has been developed: catalytic dichloro(2‐pyridinecarboxylato)gold [PicAuCl2] in the presence of an acid produces a range of imidazo[1,2‐a]pyridines in good yields starting from alkynes and 2‐aminopyridine N‐oxides. This strategy is mild and foreseen to be of particular use for the installation of stereogenic centers adjacent to the imidazo[1,2‐a]pyridine ring without loss of enantiomeric excess.
An efficient protocol has been developed for the methylenation of imidazo[1,2‐a]pyridines using dimethylacetamide (DMA) as methylene source in the presence of vanadyl acetylacetonate [VO(acac)2] as the catalyst and iodobenzene diacetate as the oxidant. The reaction involves coupling of sp3‐ and sp2‐hybridized carbons and proceeds through the formation of an iminium ion. A wide variety of imidazo[1,2‐a]pyridines were converted to bis(imidazo[1,2‐a]pyridin‐3‐yl)methanes in good to excellent yields. A gram‐scale reaction demonstrated the potential for the scale‐up processes.
The imidazo[1,2-a]pyridinium heterocyclic system was used to prepare styryl dyes. Improved synthetic methods were proposed for the parent imidazo[1,2-a]pyridines and their corresponding quaternary salts. The standard method for preparing styrylcyanines was modified for the synthesis of the target imidazo[1,2-a]pyridinium dyes. Spectral-luminescent properties of the obtained dyes in free state and in the presence of nucleic acids, BSA, and BSA/detergent system were studied. 7-[2-(4-Dihexylaminophenyl)-1-ethenyl]-2-(2,4-dimethoxyphenyl)-1-ethylimidazo[1,2-a]pyridin-1-ium iodide (SIP-8) containing C6 aliphatic tails and 2,4-methoxy substituents in the 2-phenyl ring exhibited specificity to BSA. 相似文献
A convenient gold‐catalyzed strategy for the synthesis of imidazo[1,2‐a]pyridine derivatives has been developed via gold carbene complexes. This transformation opens a new synthetic route to a variety of 3‐carbonyl‐substituted imidazo[1,2‐a]pyridines using air as oxidant affording the products in good yields.
The possibility of generating azomethine ylides from 11H-benzo[4,5]imidazo[1,2-a]indol-11-one and amino acids is shown for the first time. Based on the cycloaddition reactions of these azomethine ylides with cyclopropenes and maleimides, cyclopropa[a]pyrrolizines, 3-azabicyclo[3.1.0]hexanes, and pyrrolo[3,4-a]pyrrolizines spiro-fused with a benzo[4,5]imidazo[1,2-a]indole fragment were synthesized. Spirocyclic compounds were obtained in moderate to good yields, albeit with poor diastereoselectivity. Density functional theory calculations were performed to obtain an insight into the mechanism of the 1,3-dipolar cycloaddition of 11H-benzo[4,5]imidazo[1,2-a]indol-11-one-derived azomethine ylides to cyclopropenes. The cytotoxic activity of some of the obtained cycloadducts against the human erythroleukemia (K562) cell line was evaluated in vitro by MTS-assay. 相似文献
A direct method for the arylation of 1,2‐azolo[1,5‐a]pyridines has been developed. In the process, the fused pyridines react with aryl halides in the presence of the palladium complex Pd(OAc)2(Phen) as a catalyst and copper(I) chloride (CuCl) as a Lewis acid to form arylated derivatives. While pyrazolo[1,5‐a]pyridines and [1,2,4]triazolo[1,5‐a]pyridines are arylated at ortho‐positions of their pyridine rings using this method, in situ ring‐opening of the formed C‐7 arylated [1,5‐a]pyridine takes place to generate the 2,6‐disubstituted pyridine. Also, upon treatment with lithium diisopropylamide (LDA), C‐7 arylated pyrazolo[1,5‐a]pyridine‐3‐carboxylates react to produce diversely substituted 2,6‐disubstituted pyridines. Finally, a sequential C‐3 arylation was accomplished through a two‐step sequence involving hydrolysis of pyrazolo[1,5‐a]pyridine‐3‐carboxylates followed by the bimetallic Pd/Cu‐catalyzed decarboxylative coupling reaction with aryl bromide.
A copper(II)‐catalyzed oxidative methylene‐bridged dimerization of two analogous imidazo[1,2‐a]pyridines has been achieved using N,N‐dimethylacetamide (DMA) as solvent cum methylene source. This reaction works with a variety of substituted imidazo[1,2‐a]pyridines giving their products in moderate to good yields. Isotopic labelling experiments revealed that the methylene group in the product originates from the N,N‐dimethyl moiety of DMA.
A new copper‐catalyzed, efficient method for the synthesis of heterodiarylmethanes through the coupling of imidazo[1,2‐a]pyridines with indoles employing N,N‐dimethylformamide as a methylenating reagent has been developed. A library of 3‐(1H‐indol‐3‐ylmethyl)‐imidazo[1,2‐a]pyridine derivatives has been synthesized under aerobic reaction conditions. This protocol is also applicable for the synthesis of (4‐imidazo[1,2‐a]pyridin‐3‐ylmethyl)(phenyl)dimethylamines. The method is highly selective for the hetero‐coupling.
An efficient copper‐catalyzed oxidative coupling of imidazo[1,2‐a]pyridines with methyl ketones to directly generate structurally sophisticated 1,2‐dicarbonyl imidazo[1,2‐a]pyridine derivatives under oxidative conditions is described. The reaction proceeds in good yields using the environmental friendly molecular oxygen as the oxidant. 18O‐Labelling experiments unambiguously established that the oxygen of the dicarbonyl products originated from oxygen rather than from water.
Compared with the well‐known palladium‐catalyzed oxidative dehydrogenation coupling reactions, similar transforms initiated by copper/oxygen have attracted more and more attention. We have investigated a novel construction of heteroaromatic imidazo[1,2‐a]pyridines through copper(I) iodide/boron trifluoride etherate/oxygen‐mediated dehydrogenative reactions of aryl alkyl or alkyl alkyl ketones with 2‐aminopyridines. Four hydrogen atoms are removed and two new C N bonds are formed in one step via the imine formation and oxidative C(sp3) H functionalization.
The palladium(II)‐catalyzed hydroarylation of diphenylphosphorylallenes (via 1,2‐addition of the allenic double bond) with arylboronic acids in the presence of sodium hydroxide and oxygen is developed. The regioselectivities turn out to be well controlled, affording 2‐aryl‐3‐(diphenylphosphinyl)alkenes as the only product. Moreover, the stereoselectivities for reactions of γ‐substituted allenes can also be nicely controlled, resulting in the formation of Z‐alkenes. The reaction shows high substituent loading capability and tolerance of various substituents. A mechanism, including transmetalation of arylboronic acid with palladium halides, insertion of the 1,2‐allenic double bond to the Pd−Ar bond, and protonation to afford the final hydroarylation product is proposed.
Inter- and Intramolecular Acyl Transfer on 1(9)H-Imidazo[1,2-a]benzimidazoles The new imidazo[1,2-a]benzimidazoles ( 3 ) react with electrophiles like aroyl chlorides, isocyanates, cyanates, chloroformates and chlorothioformates to give the 9-acyl derivatives ( 4a – 1 ). At higher temperatures intermolecular acyl transfer takes place to give the l-acyl compounds ( 5a – m ). In the case of 1-carbamoyl imidazo[1,2-a]benzimidazoles ( 5 ) was observed intramolecular acyl transfer in the presence of strong bases and 1-benzimidazol-2-yl-hydantoins ( 6 ) were isolated. The structures of the prepared compounds could be inferred from their 1H and 13C n.m.r., mass spectra and were corroborated by the comparison with the data of similar derivatives as well as by chemical means. 相似文献
A highly efficient protocol for the synthesis of benzimidazole‐substituted arylboronic acids was developed via aerobic oxidative cyclization of 1,2‐aryldiamines and formyl‐substituted aryl MIDA (N‐methyliminodiacetic acid) boronates using potassium iodide as a nucleophilic catalyst. Furthermore, a one‐pot protocol for the synthesis of benzimidazole‐substituted arylboronic acids from 1,2‐phenylenediamines and formyl‐substituted arylboronic acids was developed without the isolation of any intermediates. The resulting boronic acids were further subjected to Suzuki–Miyaura coupling reactions without isolation, leading to diaryl‐substituted benzimidazoles with only one separation step.
A copper(I)‐catalysed domino transformation for the synthesis of tricyclic imidazobenzimidazole derivatives was developed. Using readily available primary propargylic amines and o‐haloarylcarbodiimides as the starting materials, a variety of substituted benzo[d]imidazo[1,2‐a]imidazoles was efficiently and selectively assembled. Further investigations indicated that the domino reaction was likely the result of a novel addition/cycloisomerisation/coupling process.
以乙醇为溶剂,在加热条件下采用LaCl3催化2-氨基吡啶、二茂铁甲醛和异氰之间的Groebke-Blackburn-Bienaym?三组分反应(GBB-3CR)合成5个二茂铁基咪唑并[1,2-a]吡啶化合物。利用核磁共振氢谱(proton magnetic resonance,1H NMR)、核磁共振碳谱(carbon-13 magnetic resonance,13C NMR)和超高效液相色谱-电喷雾离子源质谱联用仪(ultra high performance liquid chromatograph electrospray ion source mass spectrometer,UHPLC-ESI-MS)对合成产物结构进行了表征,并通过抑制HO?和还原型谷胱甘肽自由基(glutathione,GS?)引发的DNA氧化反应体系对化合物的抗氧化活性进行了检测,采用淬灭2,2?-偶氮-双-(3-乙基苯并噻唑啉-6-磺酸)二铵盐自由基(2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical,ABTS?)和二苯苦味酰肼自由基(2,2’-diphenyl-1-picrylhydrazyl,DPPH?)体系探索了化合物还原自由基的能力,进而探究了取代基对二茂铁基咪唑并[1,2-a]吡啶抗化合物氧化性能的影响。结果表明:5个目标化合物不仅能够有效地抑制自由基引发的DNA氧化反应,也能捕获自由基,是一类潜在的抗氧化剂。其中,在抑制HO?引发的DNA氧化反应体系中,5个化合物相对空白TBARS吸光度百分数可达65.4%~93.7%;在抑制GS?引发的DNA氧化反应体系中,5个化合物相对空白TBARS吸光度百分数可达25.6%~62.5%;5个二茂铁基咪唑并[1,2-a]吡啶化合物均能够捕获ABTS?和DPPH?两种自由基;双二茂铁基化合物VI抑制自由基引发的DNA氧化反应活性和捕获自由基能力优于其它化合物。 相似文献
A wide range of imidazo[1,2‐a]pyridines are accessible from cheap and readily available 2‐aminopyridines and 1,3‐dicarbonyl compounds using a unique CBrCl3/2‐aminopyridine system for bromination at the α‐carbon. 2‐Aminopyridine is not only the substrate but also acts as a bromination shuttle, transferring the bromine atom from CBrCl3 to the α‐carbon of the 1,3‐dicarbonyl. The reaction mechanism involves a series of reversible steps, including an addition reaction with cyclic transition state, to form a bromo‐hemiaminal intermediate. Isolated yields of up to 97% were obtained under mild conditions and at short reaction times in this transition metal‐free, one‐pot synthesis.
An efficient and practical copper‐catalyzed domino synthesis of benzo[4,5]imidazo[1,2‐a]pyrimidin‐4(10H)‐ones has been developed. The protocol uses N‐(2‐halophenyl)‐3‐alkylpropiolamides and cyanamide as the starting materials, inexpensive copper(I) iodide and pipecolinic acid as the catalyst and ligand, and the corresponding products were obtained in moderate to good yields.
The ionotropic GABAA receptor (GABAAR) has been proven to be an important target of atypical antipsychotics. A novel series of imidazo [1,2-a]-pyridine derivatives, as selective positive allosteric modulators (PAMs) of α1-containing GABAARs with potent antipsychotic activities, have been reported recently. To better clarify the pharmacological essentiality of these PAMs and explore novel antipsychotics hits, three-dimensional quantitative structure–activity relationships (3D-QSAR), molecular docking, pharmacophore modeling, and molecular dynamics (MD) were performed on 33 imidazo [1,2-a]-pyridines. The constructed 3D-QSAR models exhibited good predictive abilities. The dockings results and MD simulations demonstrated that hydrogen bonds, π–π stackings, and hydrophobic interactions play essential roles in the binding of these novel PAMs in the GABAAR binding pocket. Four hit compounds (DS01–04) were then screened out by the combination of the constructed models and computations, including the pharmacophore model, Topomer Search, molecular dockings, ADME/T predictions, and MD simulations. The compounds DS03 and DS04, with higher docking scores and better predicted activities, were also found to be relatively stable in the binding pocket by MD simulations. These results might provide a significant theoretical direction or information for the rational design and development of novel α1-GABAAR PAMs with antipsychotic activities. 相似文献
The paper describes the oxidative Heck arylation of various allylic amines using arylboronic acids for the preparation of tetrasubstituted alkenes. As oxidant the commercially available 2,2,6,6‐tetramethylpiperidine‐N‐oxyl (TEMPO) is used and coupling reactions occur under very mild conditions at room temperature. The densely substituted alkenes are formed in good to excellent yields with complete control of the diastereoselectivity. Substrate scope with respect to the allylic amine and the arylboronic acid is investigated.