Synthesis of Some New Pyrazolo[3,4-b]Pyridlne and Pyrazolo[3,4-d]Pyrimidine Derivatives1

Several pyrazolo[3,4-b]pyridine (3,4) and pyrazolo-[3,4-d]pyrimidine (5-13) derivatives were prepared using 5-amino-l-(5-ethyl-5H-1,2,4-triazino[5,6-b]-indol-3-yl)-lH-pyrazole-4-carbonitrile (2) . The pyridine derivatives 3 and 4 were obtained by reaction of 2 with malononitrile and ethyl cyanoacetate, respectively, while pyrimidine analogs 5-13 were synthesized cither by a one-step or multi-step sequence.     

Tricyclic heteroaromatic ring systems III. Synthesis of 1H,6H-dipyrazolo[3,4-b:3′,4′-d]pyridin-3-ones

The reaction of hydrazines with substituted ethyl 4-chloro-1H-pyrazolo[3,4-b]pyridine-3-carboxylates leads to the formation of 1H,6H-dipyrazolo[3,4-b:3,4-d]pyridin-3-ones.

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Tricyclische heteroaromatische Ringsysteme, III. Synthese von 1H,6H-Dipyrazolo[3,4,-b:3,4-d]pyridin-3-onen (Kurze Mitteilung)

Zusammenfassung Die im Titel genannten Verbindungen wurden durch die Reaktion von Hydrazinen mit substituierten Ethyl-4-chlor-1H-pyrazolo[3,4-b]pyridin-3-carboxylaten dargestellt.

     

An Efficient Synthesis of Pyrazolo[3,4-b]pyridine Derivatives in Ionic Liquid

A series of 3-methyl-1,4,6-triaryl-1H-pyrazolo[3,4-b]pyridines was synthesized via the reaction of 3-methyl-1-phenyl-1H-pyrazol-5-amine and α,β-unsaturated ketones in ionic liquid without any catalyst. This protocol has the advantages of easier work-up, milder reaction conditions, high yields and environmentally benign procedure.     

Recent progress in the chemistry of heterocycles incorporated oxazolo[4,5-b]pyridine and oxazolo[5,4-b]pyridine skeletons

Abstract

The present study describes recent advances in the chemistry of heterocycles incorporated oxazolo[4,5-b]pyridine and oxazolo[5,4-b]pyridine skeletons. The main sections included the synthesis of the investigated compounds from readily accessible aminopyridinol derivatives or aminopyridines. The reactivity of substituents attached to ring carbon or nitrogen atoms were discussed. In addition, the synthetic and biological evaluation of the inspected oxazolopyridines were highlighted. The purpose of this review is to discuss the chemistry of the title so far. The present study will support researchers in the fields of organic and medicinal chemistry to design and develop new protocols for the construction of new biological components.     

A novel synthesis of pyrazolo[3,4-b]pyridine derivatives through multi-component reaction in ionic liquid

An efficient and novel procedure for the preparation of pyrazolo[3,4-b]pyridine derivatives through multi-component reaction of aldehyde, 5-amino-3-methyl-1-phenylpyrazole and malononitrile or cyanoacetate in [bmim][BF4] is described in this paper. Advantages of the method presented here include mild conditions, high yields together with a green nature and ease of recovery and reuse of the reaction medium.     

An unexpected reaction of cyanothioacetamide： Novel preparation of pyrazolo[3,4-b]-pyridine derivatives under MWI

An unexpected multi-component reaction of cyanothioacetarnide with aldehyde and aminopyrazole under MWI was reported. Through this reaction, a series of pyrazolo[3,4-b]-pyridine derivatives was prepared in high yields via simple operational procedure.     

Unexpected formation of 4,5-dihydro-1H-pyrazolo[3,4-b]pyridine derivatives as a potent antitubercular agent and its evaluation by green chemistry metrics

Abstract

The present study describes L-hydroxy proline catalyzed unpredicted formation of 4,5-dihydro-1H-pyrazolo[3,4-b]pyridines instead of expected 4,7-dihydro-1H-pyrazolo[3,4-b]pyridines in aqueous ethanol at ambient temperature through one-pot three-component reaction. Furthermore, this protocol was evaluated using green chemistry metrics indicating green relevance of the present synthetic methodology. Most of the synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37RV strain, showing excellent results based on minimum inhibitory concentrations (MIC). Among the screened derivatives 4f, 4i, and 4j exhibited antitubercular activity with promising MIC value of 1.6?μg/mL.     

微波辐射下磷酸改性铌酸催化的香豆素修饰吡唑并[3,4-b]吡啶衍生物的高效合成

香豆素和吡唑并[3,4-b]吡啶骨架广泛存在于具有生物活性的天然化合物中,在药物化学中也被广泛用作药物核心单元,具有极其重要的作用.以磷酸改性铌酸作为催化剂,通过微波辐射下醛、香豆素衍生物、5-氨基吡唑的三组分反应一锅法高产率地合成一系列香豆素修饰的吡唑并[3,4-b]吡啶衍生物.该反应一步完成,具有催化剂和溶剂对环境友好,操作简单等优点.产物的结构经红外光谱、核磁共振谱及高分辨质谱予以确定.     

1H-Pyrazolo[3,4-b]pyridines: Synthesis and Biomedical Applications

Pyrazolo[3,4-b]pyridines are a group of heterocyclic compounds presenting two possible tautomeric forms: the 1H- and 2H-isomers. More than 300,000 1H-pyrazolo[3,4-b]pyridines have been described which are included in more than 5500 references (2400 patents) up to date. This review will cover the analysis of the diversity of the substituents present at positions N1, C3, C4, C5, and C6, the synthetic methods used for their synthesis, starting from both a preformed pyrazole or pyridine, and the biomedical applications of such compounds.     

A concise synthesis of functionalized 2,3-dihydrofuro[3,2-b], [3,2-c], and [2,3-b]pyridines

A strategy for the efficient and rapid one-pot synthesis of 2-aryl-2,3-dihydrofuro[3,2-b], [3,2-c], and [2,3-b]pyridines from readily available o-nitropicolines and aromatic aldehydes is described. The key transformation involves reaction of o-nitropicolines with aromatic aldehydes in the presence of TBAF and Hünig's base giving rise to functionalized products having molecular complexity suitable for further manipulation.     

Condensation of 2‐Pyrone with 3‐Aminopyrazolone. A Novel Synthesis of Pyrazolo[3,4‐b]pyridines

Abstract

A simple route to the preparation of new heterocyclic systems: pyrazolo[3,4‐b]pyridines from the easily available 2‐pyrone and 3‐aminopyrazolone. The structure of the compounds and the mechanism of their formation are reported.     

Facile synthesis of some novel triazolo[3,4-b]thiadiazines and triazolo[4,3-b]tetrazines

4-Amino-5-ethyl-4H-1,2,4-triazole-3-thiol was used as a key intermediate for the synthesis of triazolo[3,4-b][1,3,4]thiadiazines, triazolo[4,3-b][1,2,4,5]tetrazines and Schiff’s base via reactions with various hydrazonoyl halides and salicyaldehyde, respectively. Moreover triazolyl-N-N′-triazole derivatives were prepared from reaction of Schiff’s base with various hydrazonoyl halides. The structures of all the newly synthesized heterocyclic compounds were established by considering elemental analysis and spectral data.     

Facile and Convenient Synthesis of Pyrazole,Pyridine, Pyridazine,Pyrazolo[3,4-b]pyridine,and Pyrazolo[5,1-c][1,2,4]triazine Derivatives

Abstract

A convenient synthesis of a series of pyrazole, pyridine, pyridinethione, pyridazine, pyrazolo[3,4-b]pyridine, imidazo[1,2-a]pyrimidine, and pyrazolo[5,1-c][1 Kumar , R. 5-(1-Substituted)alkyl pyrimidine nucleosides as antiviral (herpes) agents . Curr. Med. Chem. 2004 , 11 , 2749 – 2766 . [Google Scholar] 2 Holy , A. ; Günter , J. ; Dvoráková , H. ; Masojídková , M. ; Andrei , G. ; Snoeck , R. ; Balzarini , J. ; De Clercq , E. Structure–antiviral activity relationship in the series of pyrimidine and purine N-[2-(2-phosphonomethoxy)ethyl] nucleotide analogues, 1: Derivatives substituted at the carbon atoms of the base . J. Med. Chem. 1999 , 42 , 2064 – 2086 . [Google Scholar] 4 Brandes , W. ; Daum , W. ; Krauss , P. Fungicidal oxime ethers. Ger. Patent 2,623,847, 1977; Chem. Abstr . 1978 , 88 , 120822h . [Google Scholar]]triazine derivatives incorporating a pyrimidine moiety, via the reactions of the versatile, readily accessible 3-oxo-N-(pyrimid-2-yl)butanamide with the appropriate reagents, is described.     

Molecular Hybrids of Pyazolo[3,4-b]pyridine and Triazole: Design,Synthesis and In Vitro Antibacterial Studies

Antimicrobial resistance is on the rise, and there aren’t enough new treatments to combat it. This might send the modern world back to the pre-antibiotic age. The molecular hybrids of pyrazolo[3,4-b]pyridine and triazole have been designed, synthesized, and analyzed for their drug-like molecule nature and in vitro analyses for their inhibition potentials against S. aureus and K. pneumoniae. The compounds 24 and 27 have been identified as the high potential molecules in this series based on in vitro experiments. Compound 24 has zone of inhibition values of 15 ± 0.82 mm and 14 ± 0.7 mm, whilst compound 27 has zone of inhibition values of 18 ± 0.95 mm and 16 ± 0.82 mm against S. aureus and K. pneumoniae, respectively. MIC and MIB values for compounds 24 and 27 against S. aureus and K. pneumoniae are 0.25 and 0.5, respectively.     

Synthesis,X-Ray Crystal Structure,and Computational Study of Novel Pyrazolo[3,4-B]pyridin-3-Ol Derivatives

Abstract

6-(Pyrazol-1-yl)pyrazolo[3,4-b]pyridin-3-ol (3a) was synthesized by cyclization reaction from 2,6-dichloro-4-methylnicotinonitrile. The related sulfonyl and acylated product (4–7) were obtained from the compound 3a and different sulfonyl and acyl chloride compounds. The sulfonylation of the compound 3a afforded the O1-sulfonylation, only, to give 3-substituted products 4–6. The acylation of the compound 3a gives 1,3-diacylated products 7 via N2, O1-diacylation. All compounds were characterized by spectroscopic methods and the molecular structures of 3a and 4–7 were determined by X-ray diffraction analysis. The molecular structure of 5 and 7 were studied by density functional theory (DFT) calculations, reproduced the experimental geometry. The energies of the three molecules of the tautomeric forms of the compound 3a were calculated by DFT calculations. It was shown that the 3a predominated in the gas phase. Besides, molecular electrostatic potential (MESP) and frontier molecular orbital (FMO) analysis of the compound 3a were investigated by theoretical calculations.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, tables, and figures.]     

Synthesis of Newly Substituted Pyrazoles and Substituted Pyrazolo[3,4‐b]Pyridines Based on 5‐Amino‐3‐Methyl‐1‐Phenylpyrazole

The reaction of the aminopyrazole 1 with benzenesulfonyl chloride, arenediazonium salt, chloroacetyl chloride, ethoxy methyleneamlononitrile and with ethyl 2‐cyano‐3‐ethoxyacrylate gave the substituted 3‐methyl‐1‐phenylpyrazole 2–5a,b . Compound 5b was cyclized to 6 and to 7 by treating it with AlCl₃ and with POCl₃, respectively. Compound 6 converted to 7 by boiling it in POCl₃/PCl₅. Compound 10b was produced through reaction of 9 with acetophenone. Reaction of 1 with benzylidinemalononitrile afforded 11 . New methods for preparation of 15 and 16 are described. The reaction of 8 with malononitrile, thiosemicarbazide, phenyl hydrazine and acetophenone afforded compounds 18–21 . The reaction of 21 with malononitrile gave 22 . Compounds 23–26 were produced upon reaction of 10a with malononitrile, phenyl hydrazine, thiosemicarbazide, semicarbazide and with benzaldehyde, respectively.     

Synthesis of Diversified Pyrazolo[3,4-b]pyridine Frameworks from 5-Aminopyrazoles and Alkynyl Aldehydes via Switchable C≡C Bond Activation Approaches

A cascade 6-endo-dig cyclization reaction was developed for the switchable synthesis of halogen and non-halogen-functionalized pyrazolo[3,4-b]pyridines from 5-aminopyrazoles and alkynyl aldehydes via C≡C bond activation with silver, iodine, or NBS. In addition to its wide substrate scope, the reaction showed good functional group tolerance as well as excellent regional selectivity. This new protocol manipulated three natural products, and the arylation, alkynylation, alkenylation, and selenization of iodine-functionalized products. These reactions demonstrated the potential applications of this new method.     

Multi-component reaction to access a library of polyfunctionally substituted 4,7-dihydropyrazolo[3,4-b]pyridines

A practical approach to polyfunctionally substituted 4,7-dihydropyrazolo[3,4-b]pyridine derivatives from heteroaryl hydrazine, 3-aryl-3-oxopropanenitriles and aldehydes have been described in the report. The present catalyst-free protocol involves the intermediacy of 5-aminopyrazole and α-cyanochalcone, which undergoes in situ Michael addition to afford title compounds in moderate to good yields. All the steps were conducted concomitantly to render the procedure as practical and straightforward as possible. The expeditious synthetic protocol experiment takes less than one hour and shows broad substrate scope.     

Facile Method for the Synthesis of Pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones via a Tandem Aza-Wittig Reaction

Fifteen novel pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7a–o) were designed and have been successfully synthesized via tandem aza-Wittig and annulation reactions of the corresponding iminophosphorances 5, phenylisocyanate, and substituted phenols in 60–77% isolated yields. Their structures were clearly verified by infrared (IR), ¹H NMR, electron impact–mass spectrometry (EI-MS), and elemental analysis. The results of a preliminary bioassay indicated that some compounds possess inhibition activities against the root of Brassica napus (rape) and Echinochloa crusgalli (barnyard grass) at a dosage of 100 mg/L and 10 mg/L.