Synthesis of Certain New Thiazole and 1,3,4‐Thiadiazole Derivatives via the Utility of 3‐Acetylindole

2‐(2‐(1‐(1H‐Indol‐3‐yl)ethylidene)‐hydrazinyl)‐4‐substituted 5‐(aryldiazenyl)thiazoles and 5‐((1‐(1H‐indol‐3‐yl)ethylidene)hydrazono)‐2‐substituted‐4‐phenyl‐4,5‐dihydro‐1,3,4‐thiadiazoles were synthesized via reaction of hydrazonoyl halides and 2‐(1‐(1H‐indol‐3‐yl)ethylidene)hydrazine‐1‐carbothioamide and alkyl 2‐(1‐(1H‐indol‐3‐yl)ethylidene)hydrazine‐1‐carbodithioate in ethanolic triethylamine. Structures of the newly synthesis were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic route whenever possible.     

A Simple and Efficient Process for the Synthesis of Novel Heterocycles Containing Benzofuran Moiety Using Thiocarbohydrazide as a Precursor

A simple and efficient process for the synthesis of novel heterocycles starting from thiocarbohydrazide was reported. Reaction of 2‐acetylbenzofuran ( 1 ) and thiocarbohydrazide ( 2 ) in ethanol containing acetic acid produced the corresponding thiocarbohydrazone 3 in 86% yield. Reaction of 3 and isatin ( 4 ) gave N,2‐bis(2‐oxoindolin‐3‐ylidene)hydrazine‐1‐carbothiohydrazine ( 6 ) in 65% yield, rather than the expected product, 3‐[(1‐methyl‐1‐benzofur‐2‐ylmethylidene)amino]‐1‐{[(3Z)‐2‐oxo‐2,3‐dihydro‐1H‐indol‐3‐ylidene]amino}thiourea ( 5 ). Reaction of 2‐((3‐(benzofuran‐2‐yl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)methylene)hydrazine carbothioamide ( 9 ) and chloroacetic acid or hydrazonoyl chloride 11 in basic medium gave (Z)‐2‐((E)‐((3‐(benzofuran‐2‐yl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)methylene)hydrazono)thiazolidin‐4‐one ( 10 ) or 2‐((E)‐2‐((3‐(benzofuran‐2‐yl)‐1‐ phenyl‐1H‐pyrazol‐4‐yl)methylene)hydrazinyl)‐4‐((E)‐(4‐fluorophenyl)diazenyl)‐5‐methylthiazole ( 12 ) in 62% or 74%, respectively.     

First Synthesis of Double Headed 1,2,4‐Triazino[5,6‐b]indole Acyclo C‐Nucleosides

Heterocyclization of bis(2‐oxo‐indol‐3‐ylidene)‐galactaric acid hydrazide ( 3 ) with a variety of one‐nitrogen cyclizing agents gave the corresponding 1,4‐bis{1,2,4‐triazino[5,6‐b]indol‐3‐yl}‐galacto‐tetritols 4–8 . Acetylation of the latter double headed acyclo C‐nucleosides with acetic anhydride in the presence of pyridine at ambient temperature resulted in N‐ and O‐acetylation to give the corresponding 1,2,3,4‐tetra‐O‐acetyl‐1,4‐bis{1,2,4‐triazino[5,6‐b]indol‐3‐yl}‐galacto‐tetritols 9–13 which were found to exist in centro‐symmetric zigzag conformations 20 . The assigned structures were corroborated by ¹H, ¹³C NMR as well as mass spectra.     

Synthesis of a New,Highly Fluorescent Amino Acid Derivative: N‐[(tert‐Butoxy)carbonyl]‐3‐[2‐(1H‐indol‐3‐yl)benzoxazol‐5‐yl]‐L‐alanine Methyl Ester

A simple method of synthesis of a new, highly fluorescent amino acid derivative from the simple and generally available substrates 3‐nitro‐L ‐tyrosine and 1H‐indole‐3‐carbaldehyde is described. The obtained compound, N‐[(tert‐butoxy)carbonyl]‐3‐[2‐(1H‐indol‐3‐yl)benzoxazol‐5‐yl]‐L ‐alanine methyl ester ( 4 ), possesses a high fluorescence quantum yield. The described method illustrates a new possibility of synthesis of amino acid derivatives possessing desirable photophysical properties.     

Absolute configuration of strictosidinic acid

The absolute configuration of strictosidinic acid, (2S,3R,4S)‐3‐ethenyl‐2‐(β‐d ‐glucopyranosyloxy)‐4‐{[(1S)‐2,3,4,9‐tetrahydro‐1H‐pyrido[3,4‐b]indol‐1‐yl]methyl}‐3,4‐dihydro‐2H‐pyran‐5‐carboxylate, was determined from its sodium chloride trihydrate, poly[[diaqua((2S,3R,4S)‐3‐ethenyl‐2‐(β‐d ‐glucopyranosyloxy)‐4‐{[(1S)‐2,3,4,9‐tetrahydro‐1H‐pyrido[3,4‐b]indol‐2‐ium‐1‐yl]methyl}‐3,4‐dihydro‐2H‐pyran‐5‐carboxylate)sodium] chloride monohydrate], {[Na(C₂₆H₃₂N₂O₉)(H₂O)₂]Cl·H₂O}_n. The strictosidinic acid molecule participates in intermolecular hydrogen bonds of the O—H...O and O—H...Cl types. The solid‐state conformation was observed as a zwitterion, based on a charged pyridine N atom and a carboxylate group, the latter mediating the packing through coordination with the sodium cation.     

Utility of Enaminonitriles in Heterocyclic Synthesis: Synthesis of Some New Pyrazole,Pyridine, and Pyrimidine Derivatives

The starting (1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)carbonohydrazonoyl dicyanide ( 2 ) was used as key intermediate for the synthesis of 3‐amino‐2‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐ylazo)‐[3‐substituted]‐1‐yl‐acrylonitrile derivatives ( 3 – 10 ). In addition, nitrile derivative 2 reacted with hydrazine hydrate or malononitrile to afford the corresponding 3,5‐diaminopyrazole 11 and enaminonitrile derivative 13 , respectively. On the other hand, compound 3 was subjected to react with malononitrile, acetic anhydride, triethylorthoformate, N,N‐dimethylformamide (DMF)‐dimethylacetal, thiourea, and hydroxylamine hydrchloride to afford antipyrine derivatives 16 – 21 . Moreover, the reaction of enaminonitrile 3 with carbon disulfide in pyridine afforded the pyrimidine derivative 22 , whereas, in NaOH/DMF followed by the addition of dimethyl sulphate afforded methyl carbonodithioate 24 . The reaction of enaminonitrile derivatives 3 – 5 with phenylisothiocyanate afforded the thiopyrimidine derivatives 25a – c . Finally, the enaminonitrile 4 reacted with 3‐(4‐chloro‐phenyl)‐1‐phenyl‐propenone to afford the pyridine derivative 27 . The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹³C‐NMR, ¹H–NMR, and MS).     

Synthesis of N‐[(tert‐Butoxy)carbonyl]‐3‐(9,10‐dihydro‐9‐oxoacridin‐2‐yl)‐L‐alanine,a New Fluorescent Amino Acid Derivative

A simple synthesis of a new, highly fluorescent amino acid and of its protected derivative useful in peptide studies is described. The obtained derivative, N‐[(tert‐butoxy)carbonyl]‐3‐(9,10‐dihydro‐9‐oxoacridin‐2‐yl)‐L ‐alanine ( 6 ), shows intense long‐wave absorption (above 360 nm) and emission (above 400 nm). The quantum yield of fluorescence of the investigated compound is very high, so it can serve as a sensitive analytical probe useful, e.g., in analysis of peptide conformations.     

Synthesis of 1,3,4‐Oxadiazole Acyclo C‐Nucleosides Bearing 5‐Methylthio{7‐substituted‐1,2,4‐triazolo[1,5‐d]tetrazol‐6‐yl}moieties

Oxidative cyclization of the sugar hydrazones ( 3_a‐f ) derived from {7H‐1,2,4‐triazolo[1,5‐d]tetrazol‐6‐ylsulfanyl}acetic acid hydrazide ( 1 ) and aldopentoses 2_a‐c or aldohexoses 2_d‐f with bromine in acetic acid in the presence of anhydrous sodium acetate, followed by acetylation with acetic anhydride gave the corresponding 2‐(per‐O‐acetyl‐alditol‐l‐yl)‐5‐methylthio{7H‐1,2,4‐triazolo[1,5‐d]tetrazol‐6‐yl}‐1,3,4‐oxadiazoles ( 5_a‐f ). Condensative cyclization of the sugar hydrazones ( 3_a‐f ) by heating with acetic anhydride gave the corresponding 3‐acetyl‐2‐(per‐O‐acetyl‐alditol‐1‐yl)‐2,3‐dihydro‐5‐methylthio{7‐acetyl‐1,2,4‐triazolo[1,5‐d]tetrazol‐6‐yl}‐1,3,4‐oxadiazoles ( 11_a‐f ). De‐O‐acetylation of the acyclo C‐nucleoside peracetates ( 5 and 11 ) with methanolic ammonia afforded the hydrazono lactones ( 7 ) and the acyclo C‐nucleosides ( 12 ), respectively. The structures of new oxadiazole derivatives were confirmed by analytical and spectral data.     

Synthesis of some polycyclic 1,2,4‐triazines disposing of acidic N‐H group

7‐(6‐Azauracil‐5‐yl)‐isatin 1 was converted through its thiosemicarbazone 2 to 6‐(6‐azauracil‐5‐yl)‐2,3‐dihydro‐5H‐1,2,4‐triazino[5,6‐b]indol‐3‐thione 3 and through the thiosemicarbazone of appropriate isatinic acid to 2‐(2‐thio‐6‐azauracil‐5‐yl)‐6‐(6‐azauracil‐5‐yl)‐aniline 4. The course of the cyclocondensation of this compound was studied and the reaction was found to proceed in both possible ways, resulting in a mixture of compound 3 and regioisomer 6‐(2‐thio‐6‐azauracil‐5‐yl)‐2,3‐dihydro‐5H‐1,2,4‐triazino[5,6‐b]‐indol‐3‐one 5. Substituted aniline 4 was oxidized to 2,6‐bis‐(6‐azauracil‐5‐yl)‐aniline 7 , which served for the preparation of hydrazone 8 , cyclization of which led to 1‐[2,6‐bis‐(6‐azauracil‐5‐yl)‐phenyl]‐6‐azauracil‐5‐carbonitrile 9. This is the first tricyclic 6‐azauracil with vicinal arrangement of 6‐azauracil rings.     

An experimental and theoretical approach to the molecular structure of 3‐{[4‐(3‐Methyl‐3‐phenyl‐cyclobutyl)‐thiazol‐2‐yl]‐hydrazono}‐1,3‐dihydro‐ indol‐2‐one

The title molecule, 3‐{[4‐(3‐methyl‐3‐phenyl‐cyclobutyl)‐thiazol‐2‐yl]‐hydrazono}‐1,3‐dihydro‐indol‐2‐one (C₂₂H₂₀N₄O₁S₁), was prepared and characterized by ¹H NMR, ¹³C NMR, IR, UV–visible, and single‐crystal X‐ray diffraction. The compound crystallizes in the monoclinic space group P21 with a = 8.3401(5), b = 5.6976(3), c = 20.8155(14) Å, and β = 95.144(5)°. Molecular geometry from X‐ray experiment and vibrational frequencies of the title compound in the ground state has been calculated using the Hartree–Fock with 6‐31G(d, p) and density functional method (B3LYP) with 6‐31G(d, p) and 6‐311G(d, p) basis sets, and compared with the experimental data. The calculated results show that optimized geometries can well reproduce the crystal structural parameters, and the theoretical vibrational frequencies values show good agreement with experimental data. Density functional theory calculations of the title compound and thermodynamic properties were performed at B3LYP/6‐31G(d, p) level of theory. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

Reaction of 3‐Hydroxyquinoline‐2,4‐diones with Isocyanates and Thermally Induced Transformation of the Reaction Products

3‐Hydroxyquinoline‐2,4‐diones 1 react with isocyanates to give novel 1,2,3,4‐tetrahydro‐2,4‐dioxoquinolin‐3‐yl (alkyl/aryl)carbamates 2 and/or 1,9b‐dihydro‐9b‐hydroxyoxazolo[5,4‐c]quinoline‐2,4(3aH,5H)‐diones 3 . Both of these compounds are converted, by boiling in cyclohexylbenzene solution in the presence of Ph₃P or 4‐(dimethylamino)pyridine, to give 3‐(acyloxy)‐1,3‐dihydro‐2H‐indol‐2‐ones 8 . All compounds were characterized by IR, and ¹H‐ and ¹³C‐NMR spectroscopy, as well as by EI mass spectrometry.     

Novel glycosylated carboranylquinazolines for boron neutron capture therapy of tumors: synthesis,characterization, and in vitro toxicity studies

The synthesis of a series of N‐glycosyl caboranylquinazolines is described. The condensation reaction of nitro‐acetylanthranilic acid with aminophenylcarborane gave 3‐[(o‐carboran‐1‐yl)phenyl]‐2‐methyl‐6‐nitroquinazolin‐4(3H)‐one 1 followed by reduction with Na₂S to the corresponding 6‐amino‐3‐[(o‐carboran‐1‐yl)phenyl]‐2‐methylquinazolin‐4(3H)‐one 2 . Reaction of compound 2 with D‐glucose or D‐ribose in methanol in the presence of a catalytic amount of acetic acid affords boronated N‐glycosylaminoquinazolines namely: 2‐methyl‐3‐[4‐(o‐carboran‐1‐yl)phenyl]‐6‐[N‐β‐D‐glucopyranosyl)]aminoquinazolin‐4(3H)‐one 3 or 2‐methyl‐3‐[4‐(o‐carboran‐1‐yl)phenyl]‐6‐[N‐β‐D‐ribofuranosyl)]aminoquinazolin‐4(3H)‐one 4 , respectively. Degradation of the o‐caborane cage of compounds 3 and 4 yielded highly water‐soluble compounds of sodium 2‐methyl‐3‐[4‐( nido ‐undecarborate‐1‐yl)phenyl]‐6‐[N‐β‐D‐glucopyranosyl]aminoquinazolin‐4(3H)‐one 5 and sodium 2‐methyl‐3‐[4‐( nido ‐undecarborate‐1‐yl)phenyl]‐6‐[N‐β‐D‐ribofuranosyl)]aminoquinazolin‐4(3H)‐one 6 , respectively. The structures were established on the basis of elemental analysis, NMR, IR and mass spectrometry. The in vitro toxicity test using B16 melanoma cells showed that N‐glycosyl of nido ‐undecaboranylquinazolines ( 5 and 6 ), with higher water solubility, is not toxic at boron concentration of 3000 µg boron ml⁻¹, whereas, N‐glycosyl of closo ‐carboranylquinazolines ( 3 and 4 ) has LD₅₀ > 200 µg boron ml⁻¹. The compounds described here may be considered as potential agents for BNCT. Copyright © 2008 John Wiley & Sons, Ltd.     

Cyclocondensation reaction of heterocyclic carbonyl compounds . The direction of competitive cyclocondensation between carbonyl groups of 6‐azauracile and 1,2‐dihydro‐quinoxalin‐2‐one cycles

In the article the study of cyclocondensation of 3‐[2‐amino‐3‐(3,5‐dioxo‐2,3,4,5‐tetrahydro[1,2,4]‐triazme‐6‐yl)phenyl]‐2,3‐dihydro‐quinoxalin‐2‐one 5 is described and it was found, that the reaction does not proceed by both possible directions, but only cyclization with the carbonyl group of 6‐azauracile cycle proceeds. The 6‐(3‐oxo‐3,4‐dihydro‐quinoxaline‐2‐yl)‐4H‐2,3‐dihydro[1,2,4]triazino[5,6‐b]indol‐3‐one 6 was formed in this way. This course of cyclocondensation was confirmed by the fact, that the product 6 , mentioned above, is quite different from isomeric compound 7 , prepared unambiguously by condensation of 7‐(6‐azauracile‐5‐yl)isatine 8 with o‐phenylenediamine.     

l‐Proline‐Catalyzed Knoevenagel Condensation: A Tandem Synthesis of 3‐Acetylcoumarinoindoles and Their N‐Alkyl Derivatives by Using PEG‐600 as the Reaction Medium

A tandem synthesis of 3‐acetylcoumarinoindoles 5a , 5b , 5c , 5d , 5e in the presence of catalytic amount of l ‐proline in ethanol medium is reported. l ‐proline has been utilized as an efficient and eco‐friendly catalyst for the Knoevenagel condensation of 3‐cyanoacetylindoles 1a , 1b , 1c , 1d , 1e with 2‐hydroxybenzaldehyde ( 2 ) to afford the corresponding substituted 3‐(1H‐indol‐3‐yl)2‐(2‐hydroxybenzylidene)‐3‐oxopropanenitriles 3(a–e) , which without isolation were treated with hot conc. HCl to afford 3‐acetylcoumarinoindoles 4a , 4b , 4c , 4d , 4e in high yields. Subsequently, these were reacted with dimethyl sulfate in the presence of PEG‐600 (Hyderabad, Andhra Pradesh, India) as an efficient and green solvent to afford the corresponding N‐methyl‐3‐acetylcoumarinoindoles 5a , 5b , 5c , 5d , 5e in moderate yields.     

Cyclocondensation reactions of heterocyclic carbonyl compounds XII. The double course of cyclization of 3‐(2‐aminobenzyl)‐1,2‐dihydro‐quinoxaline‐2‐one

The cyclocondensation reaction of compound 1 in boiling hydrochloric acid had an unexpected course. Instead of supposed 5,11‐dihydro‐quinoxalino[2,3‐b]quinoline 6a , 2‐(indol‐2‐yl)‐benzimidazole 4 was isolated as the major product.     

Synthesis of New Derivatives of 4‐(4,7,7‐Trimethyl‐7,8‐dihydro‐6H‐benzo[b]pyrimido[5,4‐e][1,4]thiazin‐2‐yl)morpholine

Cyclocondensation of 5‐amino‐6‐methyl‐2‐morpholinopyrimidine‐4‐thiol ( 1 ) and 2‐bromo‐5,5‐dimethylcyclohexane‐1,3‐dione ( 2 ) under mild reaction condition afforded 4,7,7‐trimethyl‐2‐morpholino‐7,8‐dihydro‐5H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐9(6H )‐one ( 3 ). The ¹H and ¹³C NMR data of compound ( 3 ) are demonstrated that this compound exists primarily in the enamino ketone form. Reaction of compound ( 3 ) with phosphorous oxychloride gave 4‐(9‐chloro‐4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐2‐yl)morpholine ( 4 ). Nucleophilic substitution of chlorine atom of compound ( 4 ) with typical secondary amines in DMF and K₂CO₃ furnished the new substituted derivatives of 4‐(4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐2‐yl)morpholine ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h ). All the synthesized products were characterized and confirmed by their spectroscopic and microanalytical data.     

Quinolone analogues 8 [1‐6]. Synthesis of 3‐aminopyridazino‐[3,4‐b]quinoxalin‐4(lH)‐one

The 3‐amino‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐one 6 and N‐(1,4‐dihydro‐1‐methyl‐4‐oxopyridazino[3,4‐b]quinoxalin‐3‐yl)carbamates 17a,b were synthesized from the 1,4‐dihydro‐1‐methyl‐4‐oxopyridazino[3,4‐b]quinoxa‐line‐3‐carboxylate 1b via the 1,5‐dihydro‐4‐hydroxy‐1‐methylpyridazino[3,4‐b]quinoxaline‐3‐carbohydrazide 13b and then 1,4‐dihydro‐1‐methyl‐4‐oxopyridazino[3,4‐b]quinoxaline‐3‐carboxazide 8 . Heating of compound 13b and arylalde‐hydes afforded the 1,4‐dihydro‐1‐methyl‐4‐oxopyridazino[3,4‐b]quinoxaline‐3‐carbo(2‐arylmethylene)hydrazides 14a‐d.     

A convenient route to pyridones,pyrazolo[2,3‐a]pyrimidines and pyrazolo[5,1‐c]triazines incorporating antipyrine moiety

Condensation of 4‐aminoantipyrine with ethyl acetoacetate, ethyl benzoylacetate, and ethyl cyanoacetate furnished the corresponding ethyl 3‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)aminoacrylate and 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide derivatives. The aminoacrylates derivatives react with acetonitrile and sodium hydride to give 2‐amino‐6‐methyl‐1‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)‐4‐pyridone. Reaction of the cyanoacetamide derivative with dimethylformamide‐dimethylacetal (DMF‐DMA) afforded 2‐cyano‐N‐[1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐pyrazol‐4‐yl]‐2‐(N,N‐dimethylamino)methylene acetamide in high yield. Treatment of the latter with 5‐aminopyrazole derivatives afforded the corresponding pyrazolo[2,3‐a]pyrimidines. 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide also reacts with heterocyclic diazonium salts to give the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine derivatives. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:508–514, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20046     

Conventional and Microwave‐Assisted Synthesis and Biological Activity Study of Novel Heterocycles Containing Pyran Moiety

Under both conventional and microwave methods, 2‐amino‐4H‐pyran‐3‐carbonitrile derivative 1 was synthesized and reacted with different reagents. Thus, 2‐amino‐4H‐pyran‐3‐carbonitrile derivative was treated with chloroacetyl chloride, phenyl isocyanate, cyanoacetic acid, benzoyl chloride, triethyl orthoformate, acetic anhydride/H₂SO₄, arylidene malononitrile, urea, and/or p‐aminosulphaguanidine producing chloroacetamide, 3‐phenylurea, cyanoacetamide, N‐benzoylpyran, ethylformimidate, pyranopyrimidin‐4‐one, pyranopyridine, pyranopyrimidin‐2‐one, and pyranopyrimidin‐2‐imine derivatives, respectively. Meanwhile, compound 1 was reacted with ethyl bromoacetate, phenacyl bromide, phthalic anhydride, different aromatic amines, and/or acetic acid/H₂SO₄ to produce 5‐aminopyrano[2,3‐b]pyrrole‐6‐carboxylate, dihydropyrano[2,3‐b]pyrrole‐6‐yl‐(phenyl)methanone, 1,3‐dioxoisoindolinyl pyran, 1,4‐dihydropyridine, and 2‐hydroxy‐1,4‐dihydropyridine derivatives, respectively. On the other hand, when compound 1 was allowed to react with maleic anhydride and/or hydrazine hydrate, pyran‐4‐oxobut‐2‐enoic acid and 3‐aminopyranopyrazole derivatives were obtained, respectively. Reaction of pyran‐4‐oxobut‐2‐enoic acid with malononitrile under different conditions gave 2‐(furan‐2‐yl)‐4H‐pyran and 2‐(4H‐pyran‐2‐yl)‐1H‐pyrrole derivatives, while condensation of 3‐aminopyranopyrazole with benzaldehyde gave 1,4‐dihydropyrano[2,3‐c]pyrazol‐3‐yl‐1‐phenylmethanimine derivative. The newly synthesized compounds were characterized by the spectroscopic tools IR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analysis. Some of these compounds have been screened in vitro for antimicrobial activity against different strains of bacteria and fungi and also were tested against two cancer cell lines: mammary gland breast cancer (MCF‐7) and colon cancer (HCT‐118).     

Solvent‐free Synthesis of 2,6‐Dihydroxy‐9H‐purin and Pteridine Derivatives

5,6‐Diaminopyrimidin‐2,4‐diol 1 was reacted with 1,4‐d ‐gluconolactone 2 , 6‐chloro‐4‐cyclopropyl‐7‐floro‐1,4‐dihydro‐1‐oxonaphthalen‐2‐carboxilic acid 4 , (3S)‐9,10‐difloro‐3,7‐dihydro‐3‐methyl‐7‐oxo‐2H‐[1,4]oxazino[2,3,4‐ij]quinolin‐6‐carboxylic acid 6 , and dimethylacetylendicarboxylate to afford 1‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)‐sorbitol 3 , 7‐chloro‐1‐cyclopropyl‐6‐flouro‐3‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)quinoline‐4(1H)‐one 5 , 9,10‐difluoro‐2,3‐dihydro‐6‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)‐3‐methyl‐[1,4]oxazine[2,3,4‐ij]quinoline‐7‐one 7 , and (2,4‐dihydroxy‐6‐oxo‐5,8‐dihydro‐6H‐pteridine‐7‐yiliden)‐acetic acid methyl ester 9 , respectively. The synthesized compounds characterized by IR, ¹H‐NMR, ¹³C‐NMR, GC‐mass, and elemental analysis.