Ring‐ring interconversions. Part 3. On the effect of the substituents on the thiazole moiety in the ring‐opening/ring‐closing reactions of nitrosoimidazo[2,1‐b][1,3]thiazoles with hydrochloric acid

The reaction of 6‐(4‐chlorophenyl)‐5‐nitrosoimidazo[2,1‐b][1,3]thiazole 1b , 6‐(4‐chlorophenyl)‐2‐methyl‐5‐nitrosoimidazo[2,1‐b][1,3]thiazole 1c , 6‐(4‐chlorophenyl)‐2,3‐dimethyl‐5‐nitrosoimidazo‐[2,1‐b][1,3]thiazole 1d and 2‐(4‐chlorophenyl)‐3‐nitrosobenzo[d]imidazo[2,1‐b][1,3]thiazole 1e with hydrochloric acid has been carried out in order to investigate the effect of substituents on the thiazole ring in a recently reported ring‐ring interconversion reaction. In every case the corresponding [1,4]‐thiazino[3,4‐c][1,2,4]oxadiazol‐3‐ones 2b‐e have been obtained. In particular, the benzoderivative 1e furnished the 4‐(4‐chlorophenyl)‐4‐hydroxy‐4H‐benzo[5,6][1,4]thiazino[3,4‐c][1,2,4]oxadiazol‐1‐one 2e , containing a new tricyclic system with a quasi‐planar geometry whose pharmacological potentialities appear promising.     

Synthesis of a Novel Triheterocyclic Framework via 1,3‐Dipolar Cycloaddition of a Nitrile Oxide with Imidazo[2,1‐b][1,3]thiazole‐3(2H)‐ones

A novel series of (9Z)‐9‐arylmethylidene‐3‐(2,6‐dichlorophenyl)‐5,6‐dihydro[1,3]thiazolo[2′,3′:2,3]imidazo [1,2‐d][1,2,4]oxadiazol‐8(9H)‐one derivatives were prepared in moderate yields by the 1,3‐dipolar cycloaddition reaction of a nitrile oxide with (2Z)‐2‐arylmethylidene‐5,6‐dihydroimidazo [2,1‐b][1,3]thiazol‐3(2H)‐ones. The reaction site of the dipolarphile is the C═N of imidazo[2,1‐b][1,3]thiazole rather than the expected C═C of the arylmethylidene. The product structures were characterized thoroughly by IR, MS, NMR spectroscopy, and elemental analysis. The results indicate that this reaction proceeds with chemoselectivity and regioselectivity.     

Synthesis of new functionalized imidazo[2,1‐b]thiazoles and thiazolo[3,2‐a]pyrimidines

5‐Oxo‐5H‐[1,3]thiazolo[3,2‐a]pyrimidine‐6‐carboxylic acid ( 4 ), and 6‐methylimidazo[2,1‐b]thiazole‐5‐carboxylic acid ( 17 ) were reacted with amines 6a‐i by the reaction with oxalyl chloride and N, N‐di methyl‐formamide as a catalyst into primary and secondary amide derivatives 7‐14 and 19‐22. From compound 24 N,N'‐disubstituted ureas 26, 27 and perhydroimidazo[1,5‐c]thiazole 29 derivatives of imidazo[2,1‐b]thiazole were prepared. By nmr analysis of compound 29 , the existence of two stereoisomers resulting from both optical, due to centre of chirality at C7′a, and conformational isomerism, due to restricted C5? N6′ bond rotation were proved.     

Synthesis and X‐ray characterization of 2,5,6‐trisubstituted imidazo[2,1‐b][1,3,4]thiadiazole derivatives

A series of 2,5,6‐trisubstituted imidazo[2,1‐b][1,3,4]thiadiazoles via Mannich reaction of imidazo[2,1‐b][1,3,4]thiadiazoles with morpholine and formaldehyde were synthesized. Structures of all the newly synthesized compounds are well supported by spectral data such as IR, NMR, Mass, and Elemental analysis. Compound 3a has been confirmed by X‐ray diffraction studies. J. Heterocyclic Chem., (2012).     

Synthesis and Structural Characterization of Pyrrole Heterocyclic Systems Bearing Amino Acid Units: Novel Pyrrol‐3‐ones,Pyrrolo[1,2‐a][3,1]benzoxazines,and Pyrrolo[2,1‐b][1,3]oxazoles

Furan‐3‐one derivatives 1 were converted into 2‐hydroxy‐pyrrole‐3‐ones 4 by reacting with various α‐ and β‐amino acids. In contrast, the reaction of furan‐3‐ones and 1‐aminocyclobutanecarboxylic acid afforded spiro‐pyrrolo[2,1‐b][1,3]oxazoles 5 via the pyrrole‐3‐one intermediate under the same reaction conditions. Some of 2‐hydroxy‐pyrrole‐3‐ones 3 derived from anthranilic acids were transformed to pyrrolo[1,2‐a][3,1]benzoxazines via intramolecular esterification.     

A new approach for the synthesis of some pyrazolo[5,1‐c]triazines and pyrazolo[1,5‐a]pyrimidines containing naphtofuran moiety

Naphtho[2,1‐b]furan‐2‐yl)(8‐phenylpyrazolo[5,1‐c][1,2,4]triazin‐3‐yl)methanone, ([1,2,4]triazolo[3,4‐c][1,2,4]triazin‐6‐yl)(naphtho[2,1‐b]furan‐2‐yl)methanone, benzo[4,5]imidazo[2,1‐c][1,2,4]triazin‐3‐yl‐naphtho[2,1‐b]furan‐2‐yl‐methanone, 5‐(naphtho[2,1‐b]furan‐2‐yl)pyrazolo[1,5‐a]pyrimidine, 7‐(naphtho[2,1‐b]furan‐2‐yl)‐[1,2,4]triazolo[4,3‐a]pyrimidine, 2‐naphtho[2,1‐b]furan‐2‐yl‐benzo[4,5]imidazo[1,2‐a]pyrimidine, pyridine, and pyrazole derivatives are synthesized from sodium salt of 5‐hydroxy‐1‐naphtho[2,1‐b]furan‐2‐ylpropenone and various reagents. The newly synthesized compounds were elucidated by elemental analysis, spectral data, chemical transformation, and alternative synthetic route whenever possible. J. Heterocyclic Chem., (2012).     

Synthesis of 6‐Aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐Aryl‐thiazolo[3,2‐b][1,2,4]triazoles

The cyclization of the derivatives of 3‐aminotriazole, 2‐(5‐substituted 4H‐1,2,4‐triazol‐3‐ylamino)‐1‐arylethanones and 2‐(4H‐1,2,4‐triazol‐3‐ylthio)‐1‐arylethanones to yield 6‐aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐aryl‐thiazolo[3,2‐b][1,2,4]triazoles has been described.     

Synthesis and Pharmacological Evaluation of Some Novel Imidazo[2,1-b][1,3,4]thiadiazole Derivatives

Synthesis of bis‐1,3‐{6′‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐2‐yl}‐1,2,2‐trimethylcyclopentane ( 3 ), bis‐1,3‐{thiadiazolo[2′,3′:2,1]imidazo[4,5‐b]quinoxalinyl}‐1,2,2‐trimethylcyclopentane ( 5 ) has been achieved by the reaction of bis‐(5′‐amino‐1′,3′,4′‐thiadiazolyl)‐1,2,2‐trimethylcyclopentane with α‐haloketones, 2,3‐dichloroquinoxaline respectively. Bromination of compound 3 furnished bis‐1,3‐{5′‐bromo‐6′‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐2‐yl}‐1,2,2‐trimethylcyclopentane ( 4 ). The structural assignment of these compounds was supported by IR, ¹H NMR and elemental analysis data. The antimicrobial, anti‐inflammatory and antifungal activities of some of the compounds have also been evaluated.     

A Facile Synthesis of Aryl‐Substituted Hydrazono‐Pyrazolyl[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin Derivatives

Some inimitable and therapeutic coumarin‐substituted fused[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadizole derivatives were synthesized by the cyclocondensation reaction of 2‐oxo‐2H‐chromene‐3‐carboxylic acid ( 1 ) and 4‐amino‐5‐hydrazinyl‐4H‐[1,2,4]‐triazole‐3‐thiol ( 2 ) by using phosphorous oxychloride as a cyclizing agent. This cyclized intermediate 3‐(3‐hydrazino‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐chromen‐2‐one ( 3 ) later condensation with various ethyl 2‐(2‐arylhydrazono)‐3‐oxobutanoates ( 4 ) in NaOAc/MeOH under reflux conditions afforded the corresponding new series of aryl‐substituted hydrazono‐pyrazolyl‐[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin derivatives ( 5 ) in good to excellent yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR and mass spectroscopic studies.     

Different patterns of supramolecular assembly in constitutionally similar 6‐arylimidazo[2,1‐b][1,3,4]thiadiazoles

Four imidazo[2,1‐b][1,3,4]thiadiazoles containing a simply‐substituted 6‐aryl group have been synthesized by reaction of 2‐amino‐1,3,4‐thiadiazoles with bromoacetylarenes using microwave irradiation and brief reaction times. 6‐(2‐Chlorophenyl)imidazo[2,1‐b][1,3,4]thiadiazole, C₁₀H₆ClN₃S, (I), 6‐(2‐chlorophenyl)‐2‐methylimidazo[2,1‐b][1,3,4]thiadiazole, C₁₁H₈ClN₃S, (II), 6‐(3,4‐dichlorophenyl)imidazo[2,1‐b][1,3,4]thiadiazole, C₁₀H₅Cl₂N₃S, (III), and 6‐(4‐fluoro‐3‐methoxyphenyl)‐2‐methylimidazo[2,1‐b][1,3,4]thiadiazole, C₁₂H₁₀FN₃OS, (IV), crystallize with Z′ values of 2, 1, 1 and 2 respectively. The molecular skeletons are all nearly planar and the dihedral angles between the imidazole and aryl rings are 1.51 (8) and 7.28 (8)° in (I), 9.65 (7)° in (II), 10.44 (8)° in (III), and 1.05 (8) and 7.21 (8)° in (IV). The molecules in (I) are linked by three independent C—H...N hydrogen bonds to form ribbons containing alternating R₂²(8) and R₄⁴(18) rings, and these ribbons are linked into a three‐dimensional array by three independent π‐stacking interactions. Both (II) and (III) contain centrosymmetric dimers formed by π‐stacking interactions but hydrogen bonds are absent, and the molecules of (IV) are linked into centrosymmetric R₂²(8) dimers by C—H...N hydrogen bonds. Comparisons are made with a number of related compounds.     

Synthesis and reactivity of some imidazo‐, triazolo‐ and tetrazolo‐isoquinoline derivatives

1‐Acetylirrüno‐3‐methyl‐1H‐isochromene‐4‐carbonitrile, 1 , reacts with glycine ethyl ester under basic conditions to give an imidazo[2,1‐a]isoquinoline derivative, while reaction with hydrazine hydrate in 1,4‐dioxane, with further chemistry, provides access to [1,2,4]triazolo[5,1‐a]isoquinoline, [1,2,4]triazolo[3,4‐a]isoquinoline and tetrazolo[5,1‐a]isoquinoline analogs. Benzene ring nitration and radical bromination of substituent methyl groups were investigated in the four tricycles, with some different positional reactivities being found. Two bromomethyl derivatives so produced were oxidised; ethyl 2‐bromomethyl‐6‐cyano‐5‐methylimidazo[2,1‐a]isoquinoline‐3‐carboxylate gave the anticipated ethyl 6‐cyano‐2‐formyl‐5‐methylimidazo[2,1‐a]isoquinoline‐3‐carboxylate (which reacted further with hydrazine to form a new system, 8,9‐dihydro‐6‐methyl‐8‐oxopyridazino[4′,5′:4,5]imidazo[2,1‐a]isoquinoline‐5‐carbonitrile), while 5‐bromomethyl‐2‐methyl[1,2,4]triazolo[5,1‐a]isoquinoline‐6‐carbonitrile unexpectedly gave directly another new system, 5,6‐dihydro‐5‐hydroxy‐2‐methyl‐7H‐pyrrolo[3,4‐c][1,2,4]triazolo[5,1‐a]isoquinolin‐7‐one.     

The Pseudo‐Michael Reaction of 2‐Hydrazinylidene‐1‐Arylimidazolidines with Diethyl Ethoxymethylenemalonate

The pseudo‐Michael reaction of 2‐hydrazinylidene‐1‐arylimidazolidines with diethyl ethoxymethylenemalonate (DEEM) was investigated. The reaction yields the chain adduct, namely diethyl{[2‐(1‐arylimidazolidin‐2‐ylidene)hydrazinyl]methylidene}propanedioates. This is contrary to the pseudo‐Michael reaction of DEEM with 1‐aryl‐4,5‐dihydro‐1H‐imidazol‐2‐amines that does not allow isolation of chain derivatives and leads to cyclic imidazo[1,2‐a]pyrimidine derivatives while even at thermodynamic control. At first cyclization of diethyl{[2‐(1‐arylimidazolidin‐2‐ylidene)hydrazinyl]methylidene}propanedioates leads to ethyl 1‐aryl‐5(1H,8H)oxo‐2,3‐dihydro‐imidazo[2,1‐c][1,2,4]triazepine‐6‐carboxylates. 1,5‐Sigmatropic shift, following the cyclization, caused isomerization of 5(1H,8H)oxo‐2,3‐dihydro‐imidazo[2,1‐c][1,2,4]triazepine‐6‐carboxylates to ethyl 1‐aryl‐5(1H)hydroxy‐2,3‐dihydroimidazo[2,1‐c][1,2,4]triazepine‐6‐carboxylates. Presence of both isomers in the reaction product was detected in the NMR spectra. The structure of all the compounds was confirmed with spectroscopic studies (¹H NMR and MS). The structure of diethyl{[2‐(1‐phenylimidazolidin‐2‐ylidene)hydrazinyl]methylidene}propanedioate was also confirmed by X‐ray crystallography. In the addition reaction, thermodynamics and HOMO–LUMO orbitals of the reactants were studied by using quantum chemical calculations.     

Synthesis of Imidazo[2,1‐b][2H‐1,3,4]thiadiazines and 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines

Imidazo[2,1‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 2‐amino‐5‐(4‐chlorophenyl)‐6H‐1,3,4‐thiadiazine with α‐haloketones. 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 4‐amino‐5‐sulfanyl‐l,2,4‐triazoles with phenacyl bromides.     

Imidazo[2,1‐b]thiazoles,imidazo[2,1‐b]imidazoles and Pyrrolo[1,2‐c]imidazoles. synthesis,structure and evaluation of benzodiazepine receptor binding

As a continuation of our studies on bicyclic heterocycles with benzodiazepine receptor affinity, derivatives with a 5:5 bicyclic skeleton, namely imidazo[2,1‐b]thiazoles, imidazo[2,1‐b]imidazoles and pyrrolo[1,2‐c]imidazoles were prepared. The compounds possessed an aromatic substituent with different spatial arrangement and distance to the bicyclic skeleton. X‐ray structure analysis was performed for Z‐2‐(4‐chlorobenzylidene)‐5,5‐diphenyl‐2,3,5,6‐tetrahydroimidazo[2,1‐b]imidazoline‐3,6‐dione ( 6a ) and 5‐amino‐6‐cyano‐7‐phenyl‐1‐oxo‐3‐thioxo‐2,3‐dihydro‐1H‐pyrrolo[1,2‐c]imidazole ( 20a ). In contrast to the previously described arylideneimidazo[2,1‐b]thiazepinones the smaller heterocyclic ring systems investigated in this study were devoid of meaningful benzodiazepine receptor affinity as well as anti‐convulsant activity.     

Facile Route to Novel Pyrazolo[3,4‐d]pyrimidine,Imidazo[1,2‐b] pyrazole,Pyrazolo[3,4‐d][1,2,3]triazine,Pyrazolo[1,5‐c][1,3,5]triazine and Pyrazolo[1,5‐c][1,3,5]thiadiazine Derivatives

A regioselective synthesis of novel pyrazolo[3,4‐d]pyrimidines, imidazo[1,2‐b]pyrazoles, pyrazolo[3,4‐d][1,2,3]triazine, pyrazolo[1,5‐c][1,3,5]triazine and pyrazolo[1,5‐c][1,3,5]thiadiazine incorporating a thiazole moiety was described via the reactions of the versatile, readily accessible 5‐amino‐3‐(phenylamino)‐N‐(4‐phenylthiazol‐2‐yl)‐1H‐pyrazole‐4‐carboxamide ( 1 ) with each of DMF‐DMA, phenylisothiocyanate, chloroacetyl chloride, phenacyl bromide, benzoylisothiocyanate and formalin, respectively. All structures of the newly synthesized compounds were elucidated by elemental analysis and spectral data.     

New heterocyclic structures. [1,2,5]Thiadiazolo[3′,4′:4,5]pyrimido-[2,1-b][1,3]thiazine and thiazolo[3,2a][1,2,5]thiadiazolo[3,4-d]pyrimidine

Derivatives of two new molecular structures, namely, 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one and 6,7-dihydro-9H-thiazolo[3,2-a][1,2,5]thiadiazolo[3,4-d][pyrimidin-9-one, and derivatives of N-substituted sulfamic acid, namely, (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-on-7-yl)sulfamic acid and (7-amino-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin-5-on-6-yl)sulfamic acid, were separated out as by-products in the reduction reaction of 8-amino-3,4-dihydro-7-nitroso-2H,6H-pyrimido[2,1- b][1,3]thiazin-6-one and 7-amino-2,3-dihydro-6-nitroso-5H-thiazolo[3,2-a]pyrimidin-5-one derivatives, respectively, with sodium hydrosulfite. A mechanism of reaction, which hypothesizes the action of sodium hydrosulfite in an asymmetic form, is proposed. The results of single-crystal X-ray investigation on 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one (R = 0.032 for 863 reflections) and (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b]- [1,3]thiazin-6-on-7-yl)sulfamic acid, sodium salt (R = 0.028 for 3507 reflections) are reported.     

The different modes of chiral [1,2,3]triazolo[5,1‐b][1,3,4]thiadiazines: crystal packing,conformation investigation and cellular activity

The crystal structures of four new chiral [1,2,3]triazolo[5,1‐b][1,3,4]thiadiazines are described, namely, ethyl 5′‐benzoyl‐5′H,7′H‐spiro[cyclohexane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate, C₁₉H₂₂N₄O₃S, ethyl 5′‐(4‐methoxybenzoyl)‐5′H,7′H‐spiro[cyclohexane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate, C₂₀H₂₄N₄O₄S, ethyl 6,6‐dimethyl‐5‐(4‐methylbenzoyl)‐6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine‐3‐carboxylate, C₁₇H₂₀N₄O₃S, and ethyl 5‐benzoyl‐6‐(4‐methoxyphenyl)‐6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine‐3‐carboxylate, C₂₁H₂₀N₄O₄S. The crystallographic data and cell activities of these four compounds and of the structures of three previously reported similar compounds, namely, ethyl 5′‐(4‐methylbenzoyl)‐5′H,7′H‐spiro[cyclopentane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate, C₁₉H₂₂N₄O₃S, ethyl 5′‐(4‐methoxybenzoyl)‐5′H,7′H‐spiro[cyclopentane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate, C₁₉H₂₂N₄O₄S, and ethyl 6‐methyl‐5‐(4‐methylbenzoyl)‐6‐phenyl‐6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine‐3‐carboxylate, C₂₂H₂₂N₄O₃S, are contrasted and compared. For both crystallization and an MTT assay, racemic mixtures of the corresponding [1,2,3]triazolo[5,1‐b][1,3,4]thiadiazines were used. The main manner of molecular packing in these compounds is the organization of either enantiomeric pairs or dimers. In both cases, the formation of two three‐centre hydrogen bonds can be detected resulting from intramolecular N—H…O and intermolecular N—H…O or N—H…N interactions. Molecules of different enantiomeric forms can also form chains through N—H…O hydrogen bonds or form layers between which only weak hydrophobic contacts exist. Unlike other [1,2,3]triazolo[5,1‐b][1,3,4]thiadiazines, ethyl 5′‐benzoyl‐5′H,7′H‐spiro[cyclohexane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate contains molecules of only the (R)‐enantiomer; moreover, the N—H group does not participate in any significant intermolecular interactions. Molecular mechanics methods (force field OPLS3e) and the DFT B3LYP/6‐31G+(d,p) method show that the compound forming enantiomeric pairs via weak N—H…N hydrogen bonds is subject to greater distortion of the geometry under the influence of the intermolecular interactions in the crystal. For intramolecular N—H…O and S…O interactions, an analysis of the noncovalent interactions (NCIs) was carried out. The cellular activities of the compounds were tested by evaluating their antiproliferative effect against two normal human cell lines and two cancer cell lines in terms of half‐maximum inhibitory concentration (IC₅₀). Some derivatives have been found to be very effective in inhibiting the growth of Hela cells at nanomolar and submicromolar concentrations with minimal cytotoxicity in relation to normal cells.     

Synthesis of 3‐substituted pyrido[4′,3′:4,5]thieno[2,3‐d]pyrimidines and related fused thiazolo derivatives

Convenient syntheses of 3‐substituted ethyl 4‐oxo‐2‐thioxo‐1,2,3,4,5,6,7,8‐octahydropyrid[4′,3′:4,5]thieno[2,3‐d]pyrimidine‐7‐carboxylates 3a, b, 6, 11–13 , ethyl 3‐methyl‐5‐oxo‐2,3,6,9‐tetrahydro‐5 H‐pyrido[4′,3′:4,5]thieno[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidine‐8‐7H‐carboxylate ( 4 ), and ethyl 2‐methyl‐5‐oxo‐2,3,6,9‐tetrahydro‐5H‐pyrido[4′,3′:4,5]thieno[2, 3‐d][1,3]thiazolo[3,2‐a]pyrimidine‐8[7H]carboxylate ( 8 ) from diethyl 2‐isothiocyanato‐4,5,6,7‐tetrahythieno[2,3‐c]pyridine‐3,6‐dicarboxylate ( 1 ) are reported. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:201–207, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10131     

Reaction of 4,5,6‐triaminopyrimidine and 2,4,5,6‐tetraaminopyrimidine with 3‐dimethylaminopropiophenones. Synthesis of new 4‐aryl‐2,3‐dihydropyrimido[4,5‐b][1,4]diazepines

Several new 6‐amino‐ and 6,8‐diamino‐4‐aryl‐2,3‐dihydropyrimido[4,5‐b][1,4]diazepines were obtained from the reaction of 4,5,6‐triaminopyrimidine 1a and 2,4,5,6‐tetraaminopyrimidine 1b with one equivalent of 3‐dimethylaminopropiophenones 2 in absolute ethanol. Structure analysis of 6‐amino‐ and 6,8‐diamino‐4‐aryl‐2,3‐dihydropyrimido[4,5‐b][1,4]diazepines 3a‐i , determined by detailed nmr measurements, reveals a high regioselectivity of this reaction.     

Synthesis of substituted pyrimido[4,5‐b] and [5,4‐c]‐[1,8]naphthyridines

Ethyl 1‐ethyl‐7‐methyl‐4‐oxo‐1,4‐dihydro[1,8]naphthyridine‐3‐carboxylate ( 1 ), precursor of nalidixic acid, has been converted in two steps through ([1,8]naphthyridin‐3‐yl)carbonylguanidine derivatives into substituted pyrimido[4,5‐b] and [5,4‐c][1,8]naphthyridines.