Synthesis of novel spiro-fused pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines

New pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines, with an associated spiro-3,3′-oxindole attachment, were prepared by three-component combinations of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1,2-dione with a pair of reactants chosen from a pyrazol-5-one, a pyrazole-5-amine, a barbituric acid, or a 6-aminouracil.     

Synthesis of 1-functionalized imidazo[1,5-а]pyrazolo[5,1-с]pyrazines

Chemistry of Heterocyclic Compounds - 4-Chloropyrazolo[1,5-a]pyrazines react with ethyl isocyanoacetate to form ethyl imidazo[1,5-a]pyrazolo[5,1-c]pyrazine-1-carboxylates, hydrolysis of which...     

Synthesis of Certain 3-Aminopyrazolo[5,4-b]pyridine and 3,4-Substituted Pyrido[2′,3′：3,4]pyrazolo[5,1-c][1,2,4]triazine Derivatives

2-Thioxo-1,2-dihydropyridine derivatives 2a, 2b were reacted with methyl iodide to give 2-methylthiopyridines 3a, 3b, which were reacted with hydrazine hydrate to produce 3-aminopyrazolo[5,4-b]pyridines 4a, 4b. Compounds 4a, 4b were diazotized to afford the corresponding diazonium salts 5a, 5b, which were reacted with some active methylene compounds 6a-6h to give the corresponding pyrido[2′,3′ ： 3,4]pyrazole[5,1-c][1,2,4]triazines 7-14.     

Synthesis of new pyrido[2′,3′:3,4]pyrazolo[5,1-c]-[1,2,4]triazin-4(6H)-one derivatives

Russian Chemical Bulletin - New pyrido[2′,3′:3,4]pyrazolo[5,1-c][1,2,4]triazin-4(6H)-one derivatives were synthesized from accessible 1,2,4-triazine and pyrazolo[5,1-c][1,2,4]triazine...     

Reactiohs with α -thiocarbamoylcinnamonitriles: Synthesis of pyrazolo [1,5-a] pyrimidines

Whereas each of α -thiocarbamoyl- and α -cyanomalononitrile derivatives 1a and 1d reacted with benzamidine (2) hydrochloride to give only 4-amino-6-(4-chlorophenyl)-2-phenyl-5-pyrimidine-carbonitrile (5a), they react with 5-amino-3-phenylpyrazole (6) to yield the two differently substituted pyrazolo[l,5-a]pyrimidines 7 and 8, respectively. Compounds 1a,c reacted also with α -haloketones to produce the substituted thiazoles 10. The structures of the newly synthesized compounds were proved by spectral studies and chemical routes.     

Facile synthesis and characterization of novel pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one and pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine incorporating 1,3-diarylpyrazole moiety

4-(3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-6-phenyl-2-thioxo-1,2-di hydro-pyridine-3-carbonitrile (1) reacted with ethyl chloroacetate (2) in ethanolic sodium acetate solution to yield the corresponding ethyl (3-cyanopyridin-2-ylsulphanyl)acetate derivative 3. Intramolecular cyclization of compound 3 was achieved by its heating in DMF containing potassium carbonate to afford the corresponding ethyl 3-aminothieno[2,3-b]pyridine-2-carboxylate derivative 4 which reacted with hydrazine hydrate in refluxing pyridine to yield the starting material 3-aminothieno[2,3-b]pyridine-2-carbohydrazide derivative 7. Compound 7 reacted with different reagents such as triethylorthoformate, formic acid, acetic acid and acetic anhydride to afford the target molecules pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives 8–10, 12 and 13 in good to excellent yields. On the other hand, pyridine-2(1H)-thione derivative 1 reacted with hydrazine hydrate in refluxing pyridine to give the other starting material 3-amino-1H-pyrazolo[3,4-b]pyridine derivative 20 which reacted with acetylacetone under reflux to afford the target molecule pyrido[2′,3′:3,4]pyrazolo[1,5-a]-pyrimidine derivative 21 in a good yield. The structures of target molecules were elucidated using elemental analyses and spectral data.     

Alkylation of 3-tert-Butylpyrimido[4′,5′:3,4]pyrazolo[5,1-c]-[1,2,4]triazine-4,10(1H,9H)-diones and -dithiones

Russian Journal of Organic Chemistry - The condensation of 7-amino-1-benzyl-3-tert-butyl-4-oxo-1,4-dihydropyrazolo[5,1-c][1,2,4]triazine-8-carbonitrile with formic acid afforded...     

Synthesis and antitumor activity of some new pyrazolo[1,5-α]pyrimidines

New series of pyrazolo[1,5-α]pyrimidine derivatives 7a-i,11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines,namely colorectal carcinoma(HCT116),prostate adenocarcinoma(PC-3) and liver carcinoma(HepG-2) using MTT cytotoxicity assay at 100 μg/mL.Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells.Whereas,compounds 7d and 11 a showed better antitumor activity than the rest of the compounds against both cell lines.A structure-activity relationship(SAR) has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data(MS,IR,~1H NMR and ~(13)C NMR) and elemental analysis.     

Synthesis,spectroscopic characterization,and in vitro antimicrobial activity of fused pyrazolo[4′,3′:4,5]thieno[3,2-d]pyrimidine

4-Amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide ( 1 ), which had been previously synthesized according to literature, was used for synthesizing pyrazolothieno-pyrimidine ( 2 ) in the presence of triethyl orthoformate and acetic acid. Chlorination of the latter compound upon reflux with phosphorus oxychloride afforded the chloropyrazolothienopyrimidine ( 3 ), which underwent heterocyclization reaction with sodium azide to produce the tetrazolo-pyrazolothienopyrimidine ( 6 ). The chloropyrimidine ( 3 ) reacted with hydrazine hydrate to give the hydrazinopyrimidine derivative ( 4 ), which in turn underwent intramolecular condensation reactions with various 1,3-dicarbonyl compounds, namely ethyl acetoacetate, ethyl benzoylacetate, ethyl cyanoacetate, acetylacetone, diethyl malonate, and ethyl (ethoxymethylene) cyanoacetate, yielding new pyrazolyl pyrazolothienopyrimidine ring systems. Also triazolopyrazolothieno-pyrimidines and benzylidene Schiff's base compounds were obtained as a result of the reactions with carbon disulfide in pyridine and benzaldehyde, respectively. The chemical structures of the newly synthesized compounds were elucidated using elemental and spectroscopic analyses (FT-IR, ¹ H-NMR, ¹³ C-NMR, and mass spectroscopy). Some of the synthesized compounds possess high antibacterial and antifungal activities.     

Synthesis of New Pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidines and Their Use in the Preparation of Tetraheterocyclic Systems

8,10-Dimethyl-3-(unsubstituted, methyl, ethyl, n-butyl, phenyl)-4-hydroxypyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidin-2(1H)-ones and 3-(2-hydroxyethyl)-2,8,10-trimethylpyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidin-4-ol were synthesized by cyclocondensation of 3-amine-4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine with ethyl malonates and α-acetyl-γ-butyrlolactone. Dichloro- and diazido- derivatives were obtained from the reaction of pyridopyrazlopyrimidine derivatives with POCl₃ followed by NaN₃. The tetrahetrocyclic systems were formed by cyclization of 4-chloro-3-(2-chloroethyl)-2,8,10-trimethylpyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine with the appropriate primary amines. The structures of all compounds were established by NMR and mass spectra.     

Synthesis and structure of antimony iodide complexes: [Ph3MeP] + 2 [SbI5]2−, [Ph3MeP] + 3 [Sb3I12]3−·Me2C=O, [Ph3MeP] + 3 [Sb3I12]3−, and [Ph3MeP] + 3 [Sb2I9]3−

Complexes with antimony-containing anions, [Ph₃MeP] ₊ ² [SbI₅]^2? (I), [Ph₃MeP] ₊ ² [Sb₃I₁₂]^3? (II), [Ph₃MeP] ₊ ³ [Sb₃I₁₂]^3? · Me₂C=O (III), and [Ph₃MeP] ₊ ³ [Sb₂I₉]^3? (IV), were synthesized by reacting triphenylmethylphosphonium iodide with antimony iodide. The central atom in the cations of the complexes has a distorted tetrahedral coordination. In the trinuclear anions of complexes II and III, each of the terminal SbI₃ groups is bound to the central Sb atom through two μ₂- and one μ₃ iodine bridges (SbSbSb angles are 103.0° and 102.2°, respectively). In the binuclear anion of complex IV, antimony atoms are linked with each other via three bridging iodine atoms.     

An efficient and solvent-free one-pot multi-component synthesis of novel highly substituted pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives catalyzed by tetramethylguanidine

Abstract

An efficient solvent-free access towards highly substituted pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives has been established through multi-component reaction of 1H‐pyrazolo[3,4‐b]pyridin‐3‐amine, aldehyde, 3-(1H-indol-3-yl)-3-oxopropanenitrile catalyzed by 1,1,3,3-tetramethylguanidine (TMG). The reaction allows the formation of one C?C and two C?N bonds with high yield. The significant features of this solvent-free reaction include mild reaction condition, readily accessible substrates, short reaction time, excellent yield, and broad substrate scopes as well as simple one-pot operation, no column chromatographic purification, which makes this strategy highly attractive.     

Fused quinoline heterocycles X. First synthesis of new four heterocyclic ring systems 10-amino-6,9-disubstituted-[1,2,4]triazino[4′,3′:1,5]pyrazolo[4,3-c]quinoline derivatives

A novel, simple, and efficient synthetic methodology for the synthesis of hitherto unreported tetracyclic 10-amino-6,9-disubstituted-[1,2,4]triazino[4′,3′:1,5]pyrazolo[4,3-c]quinolines, in one step, has been developed by coupling of various active methylene compounds with diazotized heterocyclic amines. Reacting 2,4-dichloroquinoline-3-carbonitrile (1) with cyanoacetic acid hydrazide (2) in the presence of triethylamine in refluxing MeOH gave the unexpected 3-amino-4-chloro-1H-pyrazolo[4,3-c]quinoline (4), instead of the desired tetracyclic ring system 3 (Scheme 1). Refluxing 4 with excess of cyclic secondary amines 5a–c in boiling dimethylformamide yielded the corresponding 4-amino-pyrazolo[4,3-c]quinolines 6a–c. Diazotization of compounds 4 and 6a–c with sodium nitrite and concentrated HCl at ?5?°C gave the corresponding diazonium salts 17a–d, which were then subjected to couple with different active methylene nitriles, namely, 2-cyanothioacetamide (12), ethyl cyanoacetate (13), malononitrile (14), 2-cyanoacetamide (15), and 2-cyano-N-phenylacetamide (16), in aqueous ethanol containing sodium acetate as a buffer solution. The coupling reaction of diazonium salts 17 with 12, 13, and 14 leading to the novel perianellated tetracyclic ring system 10-amino-6,9-disubstituted-[1,2,4]triazino[4′,3′:1,5]pyrazolo[4,3-c]quinolines 19, 23, and 27, respectively, in one step, is described for the first time. On the other hand, coupling reaction of diazonium salt 17a with both 15 and 16 yielded the previously unknown tetracyclic 10-amino-6-chloro-[1,2,4]triazino[4′,3′:1,5]pyrazolo[4,3-c]quinoline-9-carboxamides 28a and 28b, respectively (Scheme 6). No chromatographic techniques have been used for the purification of the products. The structures of all the newly synthesized compounds were unambiguously confirmed by spectroscopic and analytical techniques.     

[60]富勒烯[2＋3]环加成反应的研究进展

对[60]富勒烯[2＋3]环加成反应的研究进展进行了综述，并介绍了在环加成反应中使用的主要试剂及反应机理.     

Alkylation of 3‐Phenyl‐1H‐pyrazolo[4,3‐c] quinoline: Theoretical Analysis of Regioselectivity

The interaction of 3‐phenyl‐1H‐pyrazolo[4.3‐c]quinoline with alkylating agents in the presence of NaH leads mainly to N1‐substituted derivatives. The regioselectivity of the reaction has been studied using AM1 semi‐empirical calculations in the isolated molecule approximation.     

Synthesis of Some Novel Phenyl Substituted Oxothiazolidin- 1’’,3’’,4’’-thiadiazolo-[3’,4’-b]thiazoline of 3β-Substituted Cholestane

Three title compounds 4a—4c have been synthesized by the cyclodehydration of 1’-benzylidine-4’-(3β-substituted-5α-cholestane-6-yl)thiosemicarbazones 2a—2c with thioglycolic acid followed by the treatment with cold conc. H2SO4 in dioxane. The compounds 2a—2c were prepared by condensation of 3β-substituted-5α-cholestan- 6-one-thiosemicarbazones 1a—1c with benzaldehyde. These thiosemicarbazones 1a—1c were obtained by the reaction of corresponding 3β-substituted-5α-cholestan-6-ones with thiosemicarbazide in the presence of few drops of conc. HCl in methanol. The structures of the products have been established on the basis of their elemental, analytical and spectral data.     

Synthesis,Reactions, and Antiviral Activity of 1-(1H-Pyrazolo[3,4-b]pyridin-5-yl)ethanone and Pyrido[2′,3′:3,4]pyrazolo[5,1-c][1,2,4]triazine Derivatives

1-(3-Amino-6-methyl-4-pyridin-3-yl-1H-pyrazolo[3,4-b]pyridin-5-yl)ethanone (3) was obtained in very pure state and used as a good starting material for the present study. It diazotized to give the corresponding diazonium salt 9 and also reacted with phenyl isothiocyanate to give the corresponding thiourea derivative 4. Compound 4 was used for the preparation of thiazole derivatives 5–8 via the reaction with active halogen-containing compounds. On the other hand, compound 9 coupled with several active –CH₂- containing compounds to afford the corresponding triazine derivatives 10–17. Considering the data from IR, ¹ H NMR, mass spectra, and elemental analyses, the chemical structures of the newly synthesized heterocyclic compounds were elucidated. Cytotoxicity, anti-HSV1, and anti-HAV-MBB activity were evaluated for the newly synthesized heterocyclic compounds.