Microwave-prompted rapid and efficient synthesis of 3-alkyl substituted imidazo[1,5-a]pyridines

Under regular heating and microwave irradiation, 3-alkyl substituted imidazo[1,5-a] pyridines were synthesized from 2,2＇- pyridil, di-2-pyridyl ketone and aliphatic aldehydes in the presence of ammonium acetate and acetic acid. Compared to the traditional heating condition, the reaction time under microwave irradiation was shorter and 3-alkyl imidazo[1,5-a]pyddines were given in higher yield.     

Synthesis and Crystal Structure of [Ni(II)(L)(py)_3]·(py)

1 INTRODUCTION Schiff bases and their metal complexes are useful reagents in organic synthesis[1], and they have exhi- bited some biological activities as anticancer and antitumor drugs[2]. The crystal structures and physi- cal and chemical properties of many Schiff bases and their transition metals complexes have been re- ported[3~5]. Further interest in the coordination che- mistry of nickel(II) arises from the role of these complexes in several catalytic reactions, such as electrocat…     

Cs2CO3催化下多组分一锅法合成螺吲哚-三唑并[1,5-a] 嘧啶及螺吲哚-苯并咪唑并[1,2-a]嘧啶类化合物

以3-氨基-1,2,4-三唑(或2-氨基苯并咪唑)、靛红和丙二腈为原料,经三组分一锅法合成了7种新型的螺吲哚-三唑并[1,5-a]嘧啶类化合物（1a~1g）和5种新型的螺吲哚 苯并咪唑并[1,2-a]嘧啶类化合物（2a, 2c, 2d, 2e, 2g）,其结构经¹H NMR, IR和HR-MS（ESI）表征。以1a和2a的合成为例,优化了合成反应条件。结果表明：在最优条件（Cs₂CO₃ 20 mol%, EtOH为溶剂,于80 ℃反应120 min）下,1a和2a收率分别为90%和87%。     

An Efficient Synthesis of [1,2,4]Triazolo[3,2-d][1,5]benzoxazepin-2-thiones, a Kind of Novel Tricyclic O,N-Heterocycles

A series of novel tricyclic O,N-heterocycles, [1,2,4]triazolo[3,2-d][1,5]benzoxazepin-2-thiones 7 were achieved via acid-induced ring closure of the geminal arylazo isothiocyanate compounds 5 which were derived from substituted chroman-4-ones, followed by feasible ring expansion with simultaneous insertion of the nitrogen atom into the carbon skeleton. The X-ray crystal structure of 7d was also described.     

Synthesis and Crystal Structure of [Ni(Ⅱ)(L)(py)3]·(py)

The title complex, C37H34N6NiO5, has been prepared and characterized by X-ray diffraction analysis. It crystallizes in the monoclinic system, space group P21/c with a = 1.15244(8), b = 1.69679(12), c = 1.78341(13) nm, β = 102.2320(10)°, V = 3.4082(4) nm3, Z = 4, Mr = 701.41, F(000) = 1464, Dc = 1.367 g/cm3 and μ(MoKα) = 0.622 mm-1. The structure was refined to R = 0.0459 and wR = 0.1199 for 5718 observed reflections. The intramolecular hydrogen bonds in the crystal structure play important roles in the title complex's thermostability.     

Nano CaCO3:An Unique Condensation Agent for the Preparation of Monosubstituted Calix[4] arene by Ring-opening Reaction

Nano CaCO3 was used as a condensation agent in the ring-opening reaction of p-tert-butylcalix[4] arene with epichlorohydrin to afford 5,11,17,23-tetra-tert-butyl1-26,27,28-trihydroxy-25-(1′-chloro-2′-hydroxy-3′-propyl)calix(4] arene regioselectively in 52% yield,The yield was less than 2% by using normal CaCO3 instead of nano one under the same conditions.     

BrΦnsted acid-promoted ‘on-water’ C(sp^3)-H functionalization fot the synthesis of isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine derivatives targeting the SKP2-CKS1 interaction

The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules,which have showed broad and interesting biological activities.The efficient construction of such hybridized molecules and biological evaluation are of great interest to medicinal chemistry community.In this communication,we report an efficient BrΦnsted acid-promoted C(sp^3)-H functionalization approach that enables the rapid construction of biologically important isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine hybrids from 5-methyl-7-(2,4,6-trimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidine,2-formylbenzoic acid and various anilines.The title compounds were generated in high to excellent yields(up to 96%)regardless of the electronic nature and steric effects of the substituents.In this reaction,an isoindolinone scaffold,one C-C single bond,and two C-N bonds were formed simultaneously with high atom economy.In this work,we have envisioned that the methyl group linked to the electron-deficient Nheterocycles could be used as a new synthetic handle for late-state diversification and may have broad applications in the field of organic and medicinal chemistry.Besides,the title compounds have exhibited promising activity against the SKP2-CKS1 interaction.     

Synthesis of 11H-Indeno[1,2-b]quinolines via the Friedliinder Reaction

The nine new 11H-indeno[1,2-b]quinolines were synthesized in high yield with sodium ethoxide as a catalyst via the Friedlander condensation reaction, The possible reaction mechanism was proposed.     

2-(4′-正丙基苯)咪唑并[2,1-a]异喹啉的晶体结构

本文测定了新型抗早孕药物2-(4′-正丙基苯)咪唑并[2,1-a]异喹啉的晶体结构.该化合物分子式为C20H18N2,Mr = 286.38,晶体属单斜晶系,空间群为P21/n,晶胞参数为a = 7.2177(1),b = 7.8036(2),c = 27.429(1) A,β＝ 90.976(3)°,V = 1544.67(8)A3,Z = 4,Dc = 1.231 g/cm3,F(000) = 608.00,μ(Mo-Kα)=0.073mm-1,R = 0.0560,wR = 0.1440,获得25986个衍射点,其中独立衍射点3795个.在分子结构中,苯环(C(1)-C(6))与环(N(1),C(1)-C(9))以及咪唑环共平面,该平面与苯环(C(12)-C(17)所在平面的夹角为10.014°.     

Synthesis and Crystal Structure of 2-(4’-Methylphenoxy)-5,8,9-trimethyl-3-phenyl Thieno[3′,2′:5,6]pyrido[4,3-d]pyrimidin-4-(3H)-one Hydrochloride

1 INTRODUCTION Pyrido[4,3-d]pyrimidine derivatives have pharma- ceutical activity and germicidal action[1~3]. So far, hundreds of tetrahydro- and octahydro-pyrido[4,3- d]pyrimidines have been synthesized as potential diuretic, antirheumatic and bacteriostatic drugs, but only a few of fully aromatic pyrido[4,3-d] pyrimi- dines are known. An important synthetic route to synthesize fully aromatic pyrido[4,3-d]pyrimidines is the condensation reaction of 4-aminonicotinic acid and amines[4]. Ho…     

One-pot Synthesis of 3-Aminoimidazo[1,2-a]pyridines Catalyzed by Heteropolyacids

Condensation of aldehydes, isonitriles and 2‐aminopyridines in the presence of H₃PMo₁₂O₄₀ affords different derivatives of 3‐aminoimidazo[1,2‐a]pyridine in good to excellent yields.     

Scandium(III) Triflate–Catalyzed Efficient Synthesis of Substituted 1-Pyridylimidazo-[1,5-a]-pyridines

An efficient synthesis of substituted 1-pyridylimidazo-[1,5-a]-pyridines has been accomplished using scandium(III) triflate as catalyst under mild conditions in excellent yields.     

Efficient Synthesis of New Tetracyclic Benzofuro[3,2-d]-imidazo[1,2-a] pyrimidine-2,5-(1 H,3 H)-diones

The aza‐Wittig reaction of iminophosphorane ( 1 ) with aromaic isocyanates gave carbodiimides ( 2 ), which were allowed to react further with (‐amino ester in the presence of a catalytic amount of sodium ethoxide to give selectively new tetracyclic benzofuro[3,2‐d]imidazo[1,2‐a]pyrimidine‐2,5‐(1H,3H)‐diones ( 5 ) in good yields. X‐ray structure analysis of 5i verified the proposed structure and the reaction selectivity.     

Heterocycles from Pyrazoloylhydroximoyl Chloride: Synthesis of Certain Quinoxaline,Benzothiadiazine, Benzoxadiazine,Quinazolinone, Imidazo[1,2-a]pyridine,Imidazo[1,2-a]pyrimidine,Isoxazole, Pyrazolo[3,4-d]pyridazine and Pyrrolidino[3,4-d]isoxazolin-4,6-dione Derivatives

3-Ethoxycarbonyl-5-methyl-1-(4-methylphenyl)-4-pyrazoloylhydroximoyl chloride (1) reacted with o-phenylenediamine, o-aminothiophenol, o-aminophenol and methyl anthranilate to afford 3-nitrosoquinoxaline, benzothiadiazine, benzoxadiazine, and 3-hydroxyquinazoline, respectively. Imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine and isoxazole derivatives were obtained via the reaction of 1 with 2-aminopyridine, 2-aminopyrimidine and the appropriate active methylene compounds, respectively. Pyrazolo[3,4-d]pyridazines, and pyrrolidino[3,4-d]isoxazolines derivatives were also synthesized. The structures of the newly synthesized compounds were established on the basis of spectral data and alternate synthesis whenever possible.     

An Efficient One‐Pot Four‐Component Synthesis of Functionalized Imidazo[1,2‐a]pyridines

An efficient one‐pot four‐component protocol for the synthesis of imidazo[1,2‐a]pyridines was developed by condensing ethane‐1,2‐diamine ( 2 ), 1,1‐bis(methylthio)‐2‐nitroethene ( 1 ), aldehydes 3 , and activated methylene compounds in EtOH under reflux conditions (Tables 1–3). The features of this procedure are operational simplicity, good yields of products, in situ preparation of heterocyclic ketene aminals (HKA), and catalyst‐free conditions.     

Synthesis and Neurotropic Activity of New Heterocyclic Systems: Pyridofuro[3,2-d]pyrrolo[1,2-a]pyrimidines,Pyridofuro[3,2-d]pyrido[1,2-a]pyrimidines and Pyridofuro[3′,2′:4,5]pyrimido[1,2-a]azepines

Background: Neurotic disturbances, anxiety, neurosis-like disorders, and stress situations are widespread. Benzodiazepine tranquillizers have been found to be among the most effective antianxiety drugs. The pharmacological action of benzodiazepines is due to their interaction with the supra-molecular membrane GABA-a-benzodiazepine receptor complex, linked to the Cl-ionophore. Benzodiazepines enhance GABA-ergic transmission and this has led to a study of the role of GABA in anxiety. The search for anxiolytics and anticonvulsive agents has involved glutamate-ergic, 5HT-ergic substances and neuropeptides. However, each of these well-known anxiolytics, anticonvulsants and cognition enhancers (nootropics) has repeatedly been reported to have many adverse side effects, therefore there is an urgent need to search for new drugs able to restore damaged cognitive functions without causing significant adverse reactions. Objective: Considering the relevance of epilepsy diffusion in the world, we have addressed our attention to the discovery of new drugs in this field Thus our aim is the synthesis and study of new compounds with antiepileptic (anticonvulsant) and not only, activity. Methods: For the synthesis of compounds classical organic methods were used and developed. For the evaluation of biological activity some anticonvulsant and psychotropic methods were used. Results: As a result of multistep reactions 26 new, five-membered heterocyclic systems were obtained. PASS prediction of anticonvulsant activity was performed for the whole set of the designed molecules and probability to be active Pa values were ranging from 0.275 to 0.43. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures, anti-thiosemicarbazides effect as well as some psychotropic effect. The biological assays evidenced that some of the studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of compounds is low and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity it was found that the selected compounds have an activating behavior and anxiolytic effects on the models of “open field” and “elevated plus maze” (EPM). The data obtained indicate the anxiolytic (anti-anxiety) activity of the derivatives of pyrimidines, especially pronounced in compounds 6n, 6b, and 7c. The studied compounds increase the latent time of first immobilization on the model of “forced swimming” (FST) and exhibit some antidepressant effect similarly to diazepam. Docking studies revealed that compound 6k bound tightly in the active site of GABA_A receptor with a value of the scoring function that estimates free energy of binding (ΔG) at −7.95 kcal/mol, while compound 6n showed the best docking score and seems to be dual inhibitor of SERT transporter as well as 5-HT_1A receptor. Conclusions: Тhe selected compounds have an anticonvulsant, activating behavior and anxiolytic effects, at the same time exhibit some antidepressant effect.     

Studies on the Synthesis of New 3-(3,5-Diamino-1-substituted-pyrazol-4-yl)azo-thieno[2,3-b]pyridines and 3-(2-Amino-5,7-disubstituted-pyrazolo[1,5-a]pyrimidine-3-yl)azothieno[2,3-b]pyridines

Coupling the diazonium salt of 3-amino-2-cyano-4,6-dimethylthieno[2,3-b]pyridine 1 with malononitrile 2 gave 2-cyano-3-(hydrazonomalononitrile)-4,6-dimethylthieno[2,3-b]pyridine 3 which then reacted with hydrazine compounds 4a-4h to yield corresponding 2-cyano-3-(3,5-diamino-1-substituted-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 5a-5h. The 2-cyano-3-(2-amino-5,7-disubstituted-pyrazolo-[1,5-a]pyrimidine-3-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 7a-7f were obtained in good yield by the cyclocondensation reaction of 2-cyano-3-(3,5-diamino-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridine 5a with the appropriate 1,3-diketones 6a-6f under acidic condition.     

Metal cation-induced multifluorescence of azacrown-substituted (tetrafluorophenyl)imidazo[1,2-a]pyridine

ortho-Azacrown-substituted (tetrafluorophenyl)imidazo[1,2-a]pyridine (2) in an acetonitrile solution emits 380 nm light in the presence of Li⁺ cation and emits 460 nm light in the presence of Zn²⁺, Mg²⁺ or H⁺ cation. In contrast, para-azacrown-substituted analogue (1) emits three different fluorescent lights responding to Li⁺, Zn²⁺ or H⁺ cation, respectively; 388 nm light to Li⁺ cation, 433 nm light to Zn²⁺ cation or 469 nm light to H⁺ cation.     

Synthesis and Biological Evaluation of Novel 5,7-Diphenylimidazo[1,2-a]pyridine Derivatives

A series of novel 5,7-diphenylimidazo[1,2-a]pyridine derivatives was designed and synthesized. The in vitro cytotoxic activities of all the target compounds against human colorectal cancer（HT-29）, human lung can- cer（H460）, human gastric cancer（MKN45） and human breast cancer（MDA-MB-231） cell lines were evaluated. The pharmacological results indicated that most of the target compounds showed moderate to excellent activities against the tested cell lines. The most promising compound 4h（0.20, 0.006, 0.08, 0.021 μmol/L） was 2.6, 5.1, 3.6 and 21.9 times more active than EPC2407（0.52, 0.031, 0.29, 0.46 μmol/L） against HT-29, H460, MKN45 and MDA-MB-231 cell lines, respectively.     

Synthesis of Novel 1H‐Imidazol[1,2‐a]Indeno[2,1‐e]Pyridine‐6(5H)‐Ones Derivatives via a One‐Pot Four‐Component Condensation Reaction

1H‐imidazol[1,2‐a]indeno[2,1‐e]pyridine‐6(5H)‐ones derivatives were synthesized in a one‐pot four‐component condensation of corresponding aldehydes, 1,3‐indandione, diamine, and nitro ketene dithioacetal using KAl(SO₄)₂·12H₂O (alum) as nontoxic, reusable, inexpensive and easily available catalyst in good to excellent yields. This green protocol provides a powerful entry into fused polycyclic structures related to bioactive heterocycles.