One-pot four-component domino reaction for the synthesis of bifunctionalized spiro[indazolo[3,2-b]quinazoline-7,3′-indoline hybrids: A green approach

An efficient tandem route to obtain novel spiro[indazolo[3,2-b]quinazoline-7,3′-indolines has been explored. The one-step domino reaction proceeds via in situ generation of the 1H-indazol-3-amines followed by its reaction with the cyclic 1,3-dicarbonyls and isatin derivatives to furnish complex N-fused spiro-polyheterocyclic frameworks. This protocol describes a valuable route to concisely and feasibly obtain spiro[indazolo[3,2-b]quinazoline-7,3′-indolines from isatin derivatives. The present protocol is particularly attractive because of the following features: group-assisted-purification (GAP) chemistry process, low-cost solvent, convenience of operation, excellent atom economy, and high yields.     

A general route for the synthesis of pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine derivatives

Summary A facile synthesis of 8-substituted pyrimido[4,5:4,5]thieno[2,3-c]pyridazines (6a–i) has been accomplished. The sequence involves the ring closure of a heterocyclic aminonitrile precursor (3) after reaction with (dichloromethylene)-dimethylammonium chloride.

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Eine allgemeine Synthese von Pyrimido[4,5:4,5]thieno[2,3-c]pyridazin-Derivaten

Zusammenfassung Es wurde ein einfacher Syntheseweg für 8-substituierte Pyrimido[4,5:4,5]thieno-[2,3-c]pyridazine entwickelt. Die Reaktion verläuft über den Ringschluß eines heterocyclischen Aminonitrilvorläufers (3) nach Umsetzung mit Dichlormethylen-dimethylammoniumchlorid.

     

Multi-component synthesis of spiro[diindeno[1,2-b:2′,1′-e]pyridine-11,3′-indoline]-triones using zinc terephthalate metal-organic frameworks

The present article describes an efficient one-pot method for the preparation of spiro[diindeno[1,2-b:2′,1′-e]pyridine-11,3′-indoline]-trione derivatives from a three-component condensation reaction of 1,3-indandione, aromatic amines and isatins in the presence of a zinc terephthalate metal-organic framework Zn (BDC) MOF as the catalyst under solvent-free conditions. High yields, short reaction times, simple workup and environmentally benign procedure are advantages of this protocol. The Zn (BDC) MOF catalyst can be recovered and reused several times without loss of activity. The catalyst was characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infra red, X-ray powder diffraction and thermal gravimetric analysis.     

Synthesis of derivatives of the new heterocyclic system pyrimido[4′,5′:4,5]pyrimido[1,2-a]benzimidazole

3-Phenyl-5-methyl(phenyl)-1H,3H-pyrimido[4,5:4,5]pyrimido[1,2-a]benzimi-dazole-2,4-diones were obtained by the cyclization of N-phenyl-N-[3-ethoxycar-bonyl-4-methyl(phenyl)pyrimido [1,2-a]benzimidazol-2-yl]ureas by the action of potassium carbonate. 2-Methyl-5-phenyl-1H-pyrimido[4,5:4,5]pyrimido[1,2-a]benzimidazol-4-one was obtained by the reaction of N-3-ethoxycarbonyl-4-phenylpyrimido[1,2-a]benzimidazol-2-yl]-N,N-dimethylacetamidine with ammonium acetate in ethanol. The synthesized compounds are members of a new heterocyclic system. The molecular and crystal structure of the solvate of 3-phenyl-5-methyl-1H,3H-pyrimido[4,5:4,5] pyrimido[1,2-a]benzimidazole-2,4-dione with two molecules of DMF was studied by x-ray crystallographic analysis.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2587–2592, November, 1991.     

Synthesis of 2,4-disubstituted pyrimido[4,5-b]-indoles,pyrano[4′,3′:4,5]pyrrolo[2,3-d]pyrimidines and some conversions of pyrimido[4,5-d]indoles

Methods have been developed for the production of 2,4-disubstituted 5,6,7,8-tetrahydro-9H-pyrimido[4,5-b]indoles and pyrano[43:4,5]pyrrolo[2,3-d]pyrimidines. Heterocyclization reactions were carried out on 4-hydrazinopyrimido[4,5-b]indoles.A. L. Mndzhoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia, Erevan, 375014. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10. pp. 1413–1416, October, 1996. Original article submitted June 21, 1996.     

Synthesis and antitumor evaluation of novel tetrahydrobenzo[4′,5′]thieno[3′,2′:5,6]pyrimido[1,2-b]isoquinoline derivatives

In the present study, a novel 8,9,10,11-tetrahydro-7H,14H-benzo[4′,5′] thieno[2′,3′:4,5]-1,3-oxazino[3,2-b]isoquinoline-7,14-dione 5 was prepared by condensation of 2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzothiophene with homophthalic anhydride under microwave irradiation, followed by alkaline hydrolysis and cyclization using acetyl chloride. Compound 5 was further allowed to react with different nitrogen nucleophiles to get new tetrahydrobenzothienopyrimido isoquinolinone derivatives. The structures of the prepared compounds were elucidated by IR, ¹H-NMR, ¹³C-NMR, and mass spectroscopy. The newly prepared compounds were tested in vitro against a panel of two human tumor cell lines, namely, hepatocellular carcinoma (liver) HepG2, and mammary gland breast MCF-7. Almost all the tested compounds showed satisfactory activity.     

Diels-alder reactions with cyclic sulfones: VIII. Organic catalysis in the synthesis of spiro[1-benzothiophene-4,5′-pyrimidine]-2′,4′,6′-trione 1,1-dioxides and 2′-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′,6′-dione 1,1-dioxides

5-Isopropenyl-2,3-dihydrothiophene 1,1-dioxide reacted with 5-methylidenepyrimidine-2,4,6-triones and 5-methylidene-2-thioxopyrimidine-4,6-diones in the presence of chiral amines or amino acids with high regio- and stereoselectivity to give optically active derivatives of barbituric and thiobarbituric acids spirofused at the 5-position to 1-benzothiophene 1,1-dioxide fragment. The reaction of 5-isopropenyl-2,3-dihydrothiophene 1,1-dioxide with 5-(2-methoxybenzylidene)-2-thioxopyrimidine-4,6-dione (generated in situ from 2-methoxybenzaldehyde and thiobarbituric acid) in the presence of (?)-ephedrine or L-4-(tert-butyldimethylsiloxy) proline gave the corresponding 2-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′,6′-dione 1,1-dioxide with an enantiomeric excess of 80%.     

One-pot,three-component synthesis of spiro[indeno[1,2-b]quinoline-10,3′-pyrroles] via the Hantzsch-type reaction of 1H-pyrrole-2,3-diones

A new methodology for the synthesis of spiro[indeno[1,2-b]quinoline-10,3′-pyrrole] derivatives via a Hantzsch-type reaction has been developed. This process involves the one-pot, three-component reaction of a 1H-pyrrole-2,3-dione, an aminocyclohexenone and 1,3-indanedione in acetic acid at reflux. Operationally simple, metal-free reaction conditions, simplicity of product isolation and good yields are key advantages of this methodology.     

Engaging thieno[2,3-b]indole-2,3-dione for the efficient synthesis of spiro[indoline-3,4′-thiopyrano[2,3-b]indole] by reaction with N-substituted isatilidenes

A simple and efficient method, proceeding through a new mechanistic pathway, for the synthesis of spiro[indoline-3,4-thiopyrano[2.3-b]indole derivatives have been developed by exploiting the reaction of thieno[2,3-b]indole-2,3-dione with N-substituted isatilidenes. The compounds synthesized have been screened for antibacterial activity. The generality of the reaction and mechanistic rationale are presented.     

Efficient and facile synthesis of 5-arylindeno[2′,1′:5,6]pyrido[2,3-d] pyrimidine-2,4(3H)-dione and 7-arylbenzo[h]pyrimido[4,5-b]quinoline-8,10(5H,9H)-dione under mild conditions

An efficient and facile method for the synthesis of 5-arylindeno[2′,1′:5,6]pyrido[2,3-d] pyrimidine-2,4(3H)-dione and 7-arylbenzo[h]pyrimido[4,5-b]quinoline-8,10(5H,9H)-dione derivatives from the reactions of 2-arylidene-2,3-dihydroinden-1-one (or 2-arylidene-3,4- dihydronaphthalen-1(2H)-one) and 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione under mild conditions was described. This is a simple, efficient, and very rapid synthetic method, which is believed to provide a useful process for the synthesis of these fused heterocyclic compounds. The products were confirmed by infrared, ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry.     

Synthesis of novel spiro[benzo[4,5]thiazolo[3,2-a]chromeno[2,3-d]pyrimidine-14,3′-indoline]-1,2′,13(2H)-triones via three component reaction

A new and efficient method for the synthesis of hitherto unreported spiro[benzo[4,5]thiazolo[3,2-a]chromeno[2,3-d]pyrimidine-14,3′-indoline]-1,2′,13(2H)-triones was developed via the Domino Knoevenagel condensation–Michael addition–intermolecular cyclization sequences of isatin derivatives, cyclohexane-1,3-diones, and 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-ones, employing 12-tungstophosphoric acid (H₃PW₁₂O₄₀) as an effective and inexpensive catalyst.     

An efficient and convenient protocol for the synthesis of novel 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione derivatives

Abstract  An efficient and direct procedure for the synthesis of novel spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione derivatives is described. The process employs a condensation reaction of 2-aminobenzamides and isatins in the presence of a catalytic amount of KAl(SO₄)₂.12H₂O (alum) in ethanol under reflux. Graphical Abstract        

Synthesis of new pyridazino[4′,3′:4,5]-thieno[3,2-d]-1,2,3-triazine and pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine derivatives

Summary 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (2), 3-substituted 8,9-diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-ones (3a–c), 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (4), 8-chloro-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (5), 8-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazines (6a–h) and 7-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-ones(7a–c) were synthesized from 5-amino-3,4-diphenylthieno[2,3-c]pyridazine-6-carboxamide (1).

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Synthese neuer Pyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-und Pyrimido[4,5:4,5]thieno[2,3-c]pyridazin-Derivate

Zusammenfassung Folgende Verbindungen wurden ausgehend von 5-Amino-3,4-diphenylthieno[2,3-c]pyridazin-6-carboxamid (1) synthetisiert: 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-on (2), 3-substituierte 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (3a–c), 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8[7H]-on (4), 8-Chlor-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin (5), 8-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (6a–h) und 7-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (7a–c).

     

Microwave-assisted synthesis of new pyrimido[4′,5′：4,5]thiazolo[3,2-α] benzimidazol-4（3H）-one derivatives in solvent-free condition

Microwave-assisted synthesis of new 2-arylpyrimido[4′,5′：4,5]thiazolo[3,2-α]benzimidazol-4（3H）-ones from 3-aminothia- zolo[3,2-α]benzimidazol-2-earboxamide and aroyl halides in solvent-free condition is described. In comparison with classical conditions the reactions are faster and the yields are higher under microwave irradiation.     

Synthesis of novel tricyclic 2H,7H-furo[3′,4′:6,7]cyclohepta-[1,2-b]pyran system

The reaction of 8-hydroxy-1,3-dimethyl-4H-cyclohepta[c]furan-4-one with the ethoxymethylene derivatives of malononitrile or ethyl cyanoacetate in the presence of KOH gave noncyclic cyanovinyl derivatives as their potassium salts rather than the expected α-pyrone derivatives. They are smoothly cyclized to the target α-pyrones by refluxing with acid. The corresponding 3-benzamido-2H-pyran-2-ones can be obtained in a single vessel from the 2-aryl-4-ethoxymethylene-4H-1,3-oxazol-5-ones using the same scheme. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1632–1638, November, 2008.     

Alkylation of pyrimido[5′,4′:5,6]pyrido[3,2-b]indol-4-one derivatives

Alkylation of 11-benzyl-3,11-dihydro-4H-pyrimido[5′,4′:5,6]pyrido[3,2-b]indol-4-one with methyl iodide and methyl bromoacetate in DMF gave 3-alkylpyrimidopyridoindolones as the corresponding salts. The reaction in acetone in the presence of K₂CO₃ yielded 3,6-disubstitution products. Alkylation with DMF dimethyl acetal gave a mixture of the 3- and 6-alkylpyrimidopyridoindol-4-one bases. The structure of 4-oxo-4,6-dihydro-3H-pyrimido-[5′,4′:5,6]pyrido[3,2-b]indol-11-ium chloride (3b) was proved by X-ray diffraction analysis.     

One-pot three component isocyanide-based reaction: Synthesis of novel tetracyclic fused furo[2′,3′:4,5]pyrimido[2,1-b][1,3]benzothiazole

A rapid, efficient and benign protocol has been developed for the construction of potentially biologically active furo[2′,3′:4,5]pyrimido[2,1-b][1,3]benzothiazole derivatives as major products along with (3E)-3-[(alkylamino)methylene]-2H-pyrimido[2,1-b][1,3]benzothiazole-2,4(3H)-dione derivatives as minor products using a one-pot, multi-component reaction of isocyanides, aromatic aldehydes and 2-hydroxy-4H-pyrimido[2,1-b][1,3]benzothiazol-4-one. The significant features of this protocol are the readily available and low-cost starting materials, short reaction time, mild reaction conditions, high yield of products and avoidance of toxic solvents and catalysts. Structures of compounds 4b and 5a were confirmed from single crystal X-ray studies.