Synthesis and Biological Activity of 3‐Methyl‐1H‐pyrazole‐4‐carboxylic Ester Derivatives

In search of novel pyrazole derivatives with bioactivity, a series of 3‐methyl‐1H‐pyrazole‐4‐caboxylic: ester derivatives were synthesized via α‐oxoketene dithioacetals as starting material. The structures of all compounds prepared were confirmed by ^lH NMR, IR, MS and elemental analyses. Preliminary bioassays indicated that some compounds showed fungicidal activity against wheat rust, phoma asparagi and antiviral activity against TMV.     

The Synthesis and Biological Evaluation of N‐Substituted 1H‐Benzimidazol‐2‐yl‐1H‐pyrazole‐3,5‐diamines

The synthesis of 1H‐benzimidazol‐2‐yl‐1H‐pyrazole‐3,5‐diamines has been developed. Synthesized bisheteroaryls contain two privileged medicinal scaffolds, aminopyrazole and benzimidazole, with two diversity positions at N1 of benzimidazole and C3 of pyrazole, respectively. The three‐step synthesis includes the Mitsunobu N‐alkylation of benzimidazole and subsequent one‐pot formation of aminopyrazole involving substitution of methylthio groups with amine and hydrazine followed with final ring closure. Inhibitory activity toward cyclin‐dependent kinase 2/cyclin E and cytotoxicity against two cancer cell lines were evaluated for all novel pyrazoles. Two compounds showed modest cyclin‐dependent kinase inhibition activity and cytotoxicity against cancer cell lines K562 and MCF7.     

Synthesis and Nematocidal Activity of N‐Substituted 3‐Methyl‐1H‐pyrazole‐4‐carboxamide Derivatives Against Meloidogyne incognita

A series of novel pyrazole carboxamides were designed and synthesized through multi‐step reactions from ethyl acetoacetate and triethyl orthoformate, and their structures were characterized by Fourier transform infrared, ¹H‐NMR, ¹³C‐NMR, mass spectrometry, and elemental analysis. The preliminary insecticidal activity showed that some of them possessed good insecticidal activities against Meloidogyne incognita.     

An Efficient Synthesis of New 5‐(1‐Aryl‐1H‐pyrazole‐4‐yl)‐1H‐tetrazoles from 1‐Aryl‐1H‐pyrazole‐4‐carbonitriles via [3 + 2] Cycloaddition Reaction

A series of new 5‐(1‐aryl‐1H‐pyrazole‐4‐yl)‐1H‐tetrazoles 4a‐l were synthesized via [3 + 2] cycloaddition reaction from 1‐aryl‐1H‐pyrazole‐4‐carbonitriles 3a‐l , sodium azide and ammonium chloride, using dimethylformamide (DMF) as solvent, in good yields: 64–85%. The structures of these newly synthesized compounds were determined from the IR, ¹H‐ and ¹³C‐NMR spectroscopic data and elemental analyses.     

Synthesis of Isoxazole, 1, 2, 4‐Oxadiazole and (1H‐Pyrazol‐4‐yl)‐methanone Oxime Derivatives from N‐Hydroxy‐1H‐pyrazole‐4‐carbimidoyl Chloride and their Biological Activity

Some novel isoxazole‐, 1,2,4 oxadiazole‐, and (1H‐pyrazol‐4‐yl)‐methanone oxime derivatives were synthesized from N‐hydroxy‐1H‐pyrazole‐4‐carbimidoyl chloride and the structures of all products were identified by spectral data (¹H‐NMR, ¹³C‐NMR, IR, MS, and HRMS) and evaluated their antibacterial activity.     

A Simple and Efficient Synthesis of Ethyl 1‐Aryl‐4‐formyl‐1H‐pyrazole‐3‐carboxylates

A new simple and convenient method of synthesis of ethyl 1‐aryl‐4‐formyl‐1H‐pyrazole‐3‐carboxylates from aromatic amines via diazonium salts has been developed. Hydrolysis and hydrazinolyization of these compounds has been investigated.     

A Facile Route to Synthesize 1,2‐Dihydropyridine and 1,6 Pyrimidinone Analogues from 4‐Oxo‐4H‐Chromene‐3‐Carbaldehyde

This paper presents the synthetic capability and the exploitation of the 3‐formylchromones to serve as excellent precursors for the synthesis of 1,2‐dihydropyridine and 1,6 pyrimidinone analogs using N‐nucleophiles and active methylene molecules.     

Efficient Synthesis of 1‐Aryl‐4‐[(ethoxycarbonyl)oxy]‐1H‐pyrazole‐3‐carboxylates

Two‐step synthesis of N‐aryl 4‐[(ethoxycarbonyl) oxy]‐1H‐pyrazole‐3‐carboxylates is achieved starting from the commercially available ethyl 4‐chloroacetoacetate and aromatic amines. Azo coupling followed by cyclization with ethyl chloroformate–DMAP pair resulted in the formation of new 4‐oxy‐1H‐pyrazole derivatives in high yields.     

Investigation of Some Functionalization Reactions of 4‐Benzoyl‐5‐phenyl‐1‐(4‐methoxyphenyl)‐1H‐pyrazole‐3‐carbonyl Chloride and Their Antimicrobial Activity

The 1H‐pyrazole‐3‐carboxylic acid 1 was converted via reactions of its acid chloride 3 with various asymmetrical disubstituted urea and alcohol derivatives into the corresponding novel 4‐benzoyl‐N‐(N′,N′‐dialkylcarbamyl)‐1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxamide 4a , b and alkyl 4‐benzoyl‐1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxylate 7a‐c , respectively, in good yields (57%‐78%). Friedel‐Crafts reactions of 3 with aromatic compouns for 15 min.‐2 h led to the formation of the 4‐3‐diaroyl‐1‐(4‐hydroxyphenyl)‐5‐phenyl‐1H‐pyrazoles 9a‐c , 4‐benzoyl‐1‐(4‐methoxyphenyl)‐3‐aroyl‐5‐phenyl‐1H‐pyrazoles 10a , b and than from the acylation reactions of 9a‐c were obtained the 3,4‐diaroyl‐1‐(4‐acyloxyphenyl)‐5‐phenyl‐1H‐pyrazoles 13a‐d . The structures of all new synthesized compounds were established by NMR experiments such as ¹H, and ¹³C, as well as 2D COSY and IR spectroscopic data, and elemental analyses. All the compounds were evaluated for their antimicrobial activities (agar diffusion method) against eight bacteria and two yeasts.     

Synthesis,Nematocidal Activity and Docking Study of Novel Chiral 1‐(3‐Chloropyridin‐2‐yl)‐3‐(difluoromethyl)‐1H‐pyrazole‐4‐carboxamide Derivatives

A novel series of pyrazole carboxamide derivatives had been designed, synthesized and some of them exhibited good nematocidal activity.     

Synthesis and some reactions of 4‐(ethoxycarbonyl)‐1,5‐diphenyl‐1H‐pyrazole‐3‐carboxylic acid

1,5‐Diphenyl‐1H‐pyrazole‐3,4‐dicarboxylic acid‐4‐ethyl ester 2 , obtained from the 4‐ethoxycarbonyl‐5‐phenyl‐2,3‐furandione 1 and N‐benzylidene‐N′‐phenyl hydrazine, was converted via reactions of its acid chloride 3 with various alcohols or N‐nucleophiles into the corresponding ester 5 or amide derivatives 6 , respectively. In addition, 2 was decarboxylated to give ethyl 1,5‐diphenylpyrazole‐4‐carboxylate 4 . Nitrile 7 derivative of 2 was also obtained by dehydration of 6a in a mixture of SOCl₂ and DMF. While cyclocondensation reaction of 2 with hydrazine hydrate leads to the formation of pyrazolo[3,4‐d]pyridazine‐4,7‐dione 8 , the reaction of 3 with anhydrous hydrazine provided a new bis pyrazole derivative 9 .     

Synthesis and Antimicrobial Activity of 2‐(Pyridine‐3‐yl)‐4H‐chromen‐4‐one Derivatives

An efficiently synthesis of chromones via cyclodehydration of corresponding 1‐(2‐hydroxyphenyl)‐3‐(pyridine‐3‐yl)propane‐1,3‐dione is described under ultrasound irradiation. A series of novel 2‐(pyridine‐3‐yl)‐4H‐chromen‐4‐one derivatives was confirmed on the basis of ¹H‐NMR, mass, IR spectral data, and elemental analysis. The synthesized compounds were evaluated for their antibacterial and antifungal activities. Most of the compounds were found to be comparable potent than the reference standard drugs. Utilization of ultrasound irradiation, simple reaction conditions, isolation, and purification makes this manipulation very interesting from an economic and environmental perspective.     

Facile Synthesis and Antimicrobial Activity of 5‐Amino‐3‐methyl‐1‐phenyl‐1H‐thieno[3,2‐c]pyrazole‐6‐carbonitrile and Their Derivatives

5‐Amino‐thieno[3,2‐c]pyrazole derivative 2 was prepared by Gewald reaction in a one‐pot procedure. The amino group of compound 2 like primary aromatic amine formed the diazonium salt when treated with NaNO₂/HCl, followed by coupling with different nucleophiles to yield the azo coupling products 3a – d . The reactivity of 5‐amino‐thienopyrazole 2 has been investigated towards different electrophilic reagents such as aromatic aldehydes, alkyl halide, acid chloride, acid anhydride, phenyl isothiocyanate, carbon disulfide, ethyl glycinate, and thioacetamide, which afforded the reaction products 4 – 14 , respectively.     

Synthesis of pinacol esters of 1‐alkyl‐1H‐pyrazol‐5‐yl‐ and 1‐alkyl‐1H‐pyrazol‐4‐ylboronic acids

Starting from 1H‐pyrazol, a wide number of 1‐alkyl‐1H‐pyrazol‐4‐yl and 1‐alkyl‐1H‐pyrazol‐5‐ylboronic acids and their pinacol esters were synthesized and characterized. The key step in the described methodology is the regioselective lithiation of the pyrazole ring. The synthesized pinacolates are stable under prolonged storage and can be used as convenient reagents in organic synthesis.     

New Synthesis and Reactions of Ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate

Synthesis of ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate 5 has been achieved via abnormal Beckmann rearrangement of o‐chloroaldehyde 1 . Reaction of o‐aminocarbonitrile 5 with concentrated H₂SO₄ furnished expected o‐aminocarboxamide pyrazole 6 . Key intermediates o‐aminocarbonitrile 5 and o‐aminocarboxamide 6 were successfully utilized for the synthesis of pyrazolopyrimidine derivatives. The replacement of Cl in o‐chlorocarbonitrile 3 with secondary amine furnished new synthon 13 , which was further used for the synthesis of polysubstituted heterocycles. The obtained new products were well characterized by IR, ¹H and ¹³C NMR, and mass spectra.     

Synthesis and Characterization of Novel 1‐Methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazole Derivatives

A series of novel 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles was synthesized in three steps from 5‐(1‐methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones. 5‐(1‐Methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones were converted into 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles upon methylation followed by treatment with aq. KMnO₄. The reaction of 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles with Raney nickel resulted in desulphonylation to afford corresponding 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles. All the new synthesized compounds were characterized by spectral techniques.     

Synthesis and Antimicrobial Activity of New Pyrimidine Derivatives Incorporating 1H‐Tetrazol‐5‐ylthio Moiety

In this study, some new 4,6‐dimethoxy pyrimidine derivatives were synthesized. 2‐Amino‐4,6‐dimethoxy‐5‐thiocyanatopyrimidine ( 2 ) was synthesized by a reaction of 2‐amino‐4,6‐dimethoxypyrimidine with KSCN and was converted into 2‐amino‐5‐(1H‐tetrazol‐5‐ylthio)‐4,6‐dimethoxypyrimidine ( 4 ) by treatment with NaN₃ in the presence of NH₄Cl in DMF. Then, 1,5‐disubstitute tetrazole compounds were obtained from 4 by the alkylation reaction. In addition, some 2‐chloro‐4,6‐dimethoxy‐5‐substitute‐pyrimidines were synthesized by the diazotization method. The structures of these compounds were established on the basis of IR, ¹H NMR, APT, and HRMS spectral data and were evaluated for antibacterial activities against various bacterial strains. The results showed that some of these compounds exhibited good antibacterial activity as that of standard antibiotics Penicillin, Ampicillin, and Erythromycin.     

Synthesis,Characterization, and In Vitro Antimicrobial Activity of a New Class of 7‐Substituted Amino‐2‐phenyl‐3H‐pyrimido[4,5‐d]pyrimidin‐4‐one

A new class of pyrimido pyrimidine derivatives that exhibits in vitro antimicrobial activity was synthesized. The protection of amino group in the compound 1 with acetic anhydride, followed by the reaction with POCl₃, gave 3 . The reaction of 3 with different substituted phenyl methanediamine in dry TEA under inert atmosphere led to the formation of 4 . Deprotection of 4 followed by refluxion with different acid chlorides yielded title compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l , 6m in good yields. The identities of these compounds were confirmed following elemental analysis, IR, ¹H, ¹³C NMR, and mass spectral studies. All the title compounds exhibited pronounced in vitro antibacterial and antifungal activities.     

Design,Synthesis, Characterization,and Antimicrobial Evaluation of Novel 2‐(3, 5‐di methoxy‐4‐((1‐aryl‐1H‐1, 2, 3‐triazole‐4‐yl) methoxy) phenyl) benzo[d]thiazoles

A series of 12 new 2‐(3, 5‐dimethoxy‐4‐((1‐Aryl‐4H‐1, 2, 3‐triazol‐4‐yl) methoxy) phenyl) benzo[d]thiazoles have been synthesized from the reaction of 4‐hydroxy‐3, 5‐dimethoxybenzaldehyde, o‐amino thiophenol, propargyl bromide, and different substituted aromatic azides using “click chemistry”. The structures of these compounds were established on the basis of Fourier Transform infrared, ¹H NMR, ¹³C–NMR, and mass spectral analysis. Compounds ( 6a–l ) were screened for in vitro antimicrobial activity.