Hexahydrospiro‐pyrazolo[3,4‐b]pyridine‐4,1′‐pyrrolo[3,2,1‐ij]quinolines Derived from 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione

The tricyclic isatin, 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione ( 1 ), reacts with a combination of an aryl cyanomethyl ketone 8 and a 5‐amino‐1‐arylpyrazole 7 to generate spirocyclic products 9 .     

Spiro[pyrido[3,2,1‐ij]pyrimido[4,5‐b]quinoline‐7,5′‐pyrrolo[2,3‐d]pyrimidines] and Spiro[pyrimido[4,5‐b]quinoline‐5,1′‐pyrrolo[3,2,1‐ij]quinolines] Derived from 5,6‐Dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione

Reaction of 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione ( 1 ) with two equivalents of some 6‐aminouracils (or 6‐amino‐2‐thiouracil) generates spirocyclic tetrahydrobenzo[if]quinolizines ( 7 ). The one‐pot, three‐component reaction of amido ketone ( 1 ) with 6‐aminouracil (or 6‐amino‐2‐thiouracil) and a cyclic six‐membered 1,3‐diketone produces spirocyclic tetrahydropyrrolo[3,2,1‐ij]quinolinones ( 15 ).     

Preparation of 2,3‐dihydro‐1H,5H‐pyrido[3,2,1‐ij]quinoline‐1,5‐dione derivatives

The 2,3‐dihydro‐7‐methyl‐1H,5H‐pyrido[3,2,1‐ij]quinoline‐1,5‐dione derivatives 9 and 10 were prepared from 3‐(5,7‐dimethoxy‐4‐methyl‐2‐oxo‐2H‐quinolin‐1‐yl)propionitrile ( 6 ). Cyclodehydration of the amide 8 gave 1,2‐dihydro‐7,9‐dimethoxy‐6‐methylpyimido[1,2‐a]quinolin‐3‐one ( 11 ).     

An Efficient Synthesis of 1′,7′,8′,9′‐Tetrahydrospiro[indoline‐3,4′‐pyrazolo[3,4‐b]quinoline]‐2,5′(6′H)‐dione Derivatives in Aqueous Medium

An efficient and green reactions of isatins, 3‐amine‐1H‐pyrazole (5‐methyl‐1H‐pyrazol‐3‐amine) and 1,3‐diketone in aqueous medium for the synthesis of novel 1′,7′,8′,9′‐tetrahydrospiro[indoline‐3,4′‐pyrazolo[3,4‐b]quinoline]‐2,5′(6′H)‐dione derivatives were reported in this research. The advantages of this reaction are simple operation, mild‐reaction conditions, wide scope substrate, high yields, and friendly environment. The products were confirmed by IR, ¹H NMR, ¹³C NMR, and HRMS.     

Synthesis of new guanidine derivatives from 2′,3′,4′,9′-tetrahydrospiro[piperidine-4,1′-[1H]pyrido[3,4-b]indole]

The reaction of the isothiourea derivative 2 with methylaminc or pyrrolidine resulted in guanidines 3a-3b . Using hydrazine under the same conditions the tetrazole derivative 4 was obtained. On reacting 2 with piperidine, morpholine, methylhydrazine, phenylhydrazine, hydroxylamine or sodium hydroxide, cycliza-tion took place leading to the novel 4-cyanimino-1,2,3,4,6,7,12,12b-octahydro-3,12b-ethanopyrim-ido[1′,6′:1,2]pyrido[3,4-b]indole ( 5 ). Some structural aspects of 5 and other model compounds were analysed mainly by ¹³C nmr spectroscopy.     

Synthesis of pyrrolo[3′,4′:2,3]azepino[4,5,6‐cd]indole‐8,10‐diones

3‐Amino‐4‐(3‐indolyl)pyrrolin‐2,5‐diones are condensed with various aldehydes and ketones to the cor responding imines. Under Pictet‐Spengler conditions, the latter do not cyclize to pyrrolo‐β‐carbolines, but readily yield pyrrolo[3′,4′:2,3]azepino[4,5,6‐cd]indole‐8,10‐diones.     

Compounds in the pyrrolo[3′,4′:4,5] pyrrolo[3,4-b]indole series

Compounds in the new pyrrolo[3′,4′:4,5]pyrrolo[3,4-b]indole series have been produced by an imide cyclization of appropriate derivatives of pyrrolo[3,4-b]indole.     

Two similarly substituted benzo[h]pyrazolo[3,4‐b]quinoline‐5,6(10H)‐diones: supramolecular structures in two and three dimensions

The molecules of 8‐methyl‐7,10‐diphenyl‐5H‐benzo[h]pyrazolo[3,4‐b]quinoline‐5,6(10H)‐dione, C₂₇H₁₇N₃O₂, (I), are weakly linked into chains by a single C—H...O hydrogen bond, and these chains are linked into sheets by a π–π stacking interaction involving pyridyl and aryl rings. In 8‐methyl‐7‐(4‐methylphenyl)‐10‐phenyl‐5H‐benzo[h]pyrazolo[3,4‐b]quinoline‐5,6(10H)‐dione, C₂₈H₁₉N₃O₂, (II), the molecules are linked into a three‐dimensional framework structure by a combination of C—H...N, C—H...O and C—H...π(arene) hydrogen bonds, together with a π–π stacking interaction analogous to that in (I).     

Synthesis of a New Imidazo[4′,5′:3,4]pyrazolo[5,1‐c][1,2,4]triazine‐4,8‐dione Heterocyclic System

A novel imidazo[4′,5′:3,4]pyrazolo[5,1‐c][1,2,4]triazine‐4,8‐dione heterocyclic system was synthesized starting from available 4‐amino‐6‐tert‐butyl‐3‐methylthio‐1,2,4‐triazin‐5(4H)‐one in four steps with 28% overall yield.     

Synthesis and reactivity of 1‐amino‐4‐methyl‐3,4‐dihydro‐5H‐pyrazolo[3′,4′:4,5]pyrimido[1,6‐a]benzoimidazolo‐5‐one

Pyrimido[2“,1”:5′,6′]pyrazolo[3′,4′:4,5]‐pyrimido[1,6‐a]benzoimidazoloe‐2,8(1H,7H)‐diones, and [1,2,4]‐triazino‐[3“,4”:5′,6′]pyrazolo[3′,4′:4,5]pyrimido[1,6‐a]benzimidazol‐8(7H)‐ones were synthesized in a good yields via 1‐amino‐4‐methyl‐3,4‐dihydro‐5H‐pyrazolo[3′,4′:4,5]pyrimido[1,6‐a]benzoimidazolo‐5‐one and the appropriate active methylene compounds. Structures of the newly synthesized compounds were elucidated on the basis of elemental analyses, spectral data, and alternative synthesis methods whenever possible.     

Two polymorphs of 4‐propyl‐3,4‐dihydro‐2H‐naphtho[1,2‐b]pyran‐5,6‐dione

Two polymorphs of the title compound, C₁₆H₁₆O₃, have been obtained from the same solution. One polymorph, (I_m), crystallizes in the monoclinic space group P2₁, while the other, (I_o), crystallizes in the orthorhombic space group P2₁2₁2₁. The cell constants of the two polymorphs are surprisingly similar. Whereas the a and b axes are equal in the two structures, the c axis in (I_o) is twice as long as that in (I_m). The monoclinic angle β is 95.084 (9)° compared with 90° in the orthorhombic crystal system. The cell volume of (I_m) is almost exactly half of the cell volume of (I_o). The packing motifs are also very similar in the two structures. However, whereas the molecules in (I_m) are related by a twofold screw axis just in the direction of the b axis, in (I_o) there are twofold screw axes along all three directions of the unit cell.     

Synthesis of Pyrido[2′,3′: 3,4]pyrazolo[1,5‐a]pyrimidine,Pyrido[2′,3′:3,4]pyrazolo[5,1‐c][1,2,4]triazine,and Pyrazolyl Oxadiazolylthieno[2,3‐b]pyridine Derivatives

6‐(2‐Thienyl)‐4‐(trifluoromethyl)‐1H‐pyrazolo[3,4‐b]pyridine‐3‐amine reacted with different active methylene compounds to afford pyridopyrazolopyrimidine derivatives. On the other hand, it reacted with some halo compounds to give the imidazo[1′,2′:1,5]pyrazolo[3,4‐b]pyridine derivatives. Also, it diazotized to give the corresponding diazonium chloride that is coupled with several active methylene compounds to give the corresponding triazine derivatives. Furthermore, compound 3‐amino‐6‐(2(thienyl)‐4‐(trifluoromethyl)thieno[2,3‐b]pyridine‐2‐carbohydrazide reacted with some β‐dicarbonyl compounds and some sulfur‐containing compounds to afford the corresponding pyrazolyl oxadiazolylthieno[2,3‐b]pyridine derivatives.     

2,3,3′,6‐Tetra‐O‐acetyl‐4,1′,6′‐trichloro‐4,1′,4′,6′‐tetradeoxygalactosucrose

At 160 K, one of the Cl atoms in the furanoid moiety of 3‐O‐acetyl‐1,6‐di­chloro‐1,4,6‐tri­deoxy‐β‐d ‐fructo­furan­osyl 2,3,6‐tri‐O‐acetyl‐4‐chloro‐4‐deoxy‐α‐d ‐galacto­pyran­oside, C₂₀H₂₇­Cl₃O₁₁, is disordered over two orientations, which differ by a rotation of about 107° about the parent C—C bond. The conformation of the core of the mol­ecule is very similar to that of 3‐O‐acetyl‐1,4,6‐tri­chloro‐1,4,6‐tri­deoxy‐β‐d ‐tagato­furanos­yl 2,3,6‐tri‐O‐acetyl‐4‐chloro‐4‐deoxy‐α‐d ‐galacto­pyran­oside, particularly with regard to the conformation about the glycosidic linkage.     

Synthesis and reactions of 11H‐benzo[b]pyrano[3,2‐f]indolizines an pyrrolo[3,2,1‐ij]pyrano[3,2‐c]quinolines

2‐Methyl‐3H‐indoles 1 cyclize with two equivalents of ethyl malonate 2 to form 4‐hydroxy‐11H‐benzo[b]pyrano[3,2‐f]indolizin‐2,5‐diones 3, whereas 2‐mefhyl‐2,3‐dihydro‐1H‐indoles 9 give under similar conditions regioisomer 8‐hydroxy‐5‐methyl‐4,5‐dihydro‐pyrrolo[3,2,1‐ij]pyrano[3,2‐c]quinolin‐7,10‐diones 10 . The pyrone rings of 3 and 9 can be cleaved either by alkaline hydrolysis to give 7‐acetyl‐8‐hydroxy‐10H‐pyrido[1,2‐a]indol‐6‐ones 4 or 5‐acetyl‐6‐hydroxy‐2‐methyl‐1,2‐dihydro‐4H‐pyrrolo‐[3,2,1‐ij]quinolin‐4‐ones 11 , respectively. Chlorination of 3 and 9 with sulfurylchloride gives under subsequent ring opening 7‐dichloroacetyl‐8‐hydroxy‐10H‐pyrido[1,2‐a]indol‐6‐ones 5 or 5‐dichloracetyl‐6‐hydroxy‐2‐methyl‐1,2‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinolin‐4‐ones 12 . The dichloroacetyl group of 5 can be reduced with zinc to 7‐acetyl‐8‐hydroxy‐10H‐pyrido[1,2‐a]indol‐6‐ones 7. Treatment of the acetyl compounds 4, 7 and 11 with 90% sulfuric acid cleaves the acetyl group and yields 8‐hydroxy‐10H‐pyrido[1,2‐a]‐indol‐6‐ones 6 and 8 , and 6‐hydroxy‐2‐methyl‐1,2‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinolin‐4‐ones 13 . Reaction of dichloroacetyl compounds 12 with sodium azide yields 6‐hydroxy‐2‐methyl‐5‐(1H‐tetrazol‐5‐ylcarbonyl)‐1,2‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinolin‐4‐ones 14 via intermediate geminal diazides.     

Polycyclic pyridazines. II [3]. Synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrid-azine derivatives from dimethyl pyrazolo[3,4-d]pyrid-azine-5,6-dicarboxylates as the key intermediates

The synthesis of the novel pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyridazine ring system and some of its derivatives has been accomplished such as 4-amino-1-phenyl-5,8-dioxo-, 4-amino-5,8-dioxo-, 1-phenyl-5,8-dioxo-, 5,8-dioxo-, 5,8-dichloro-1-phenyl-, 5-ethoxy-1-phenyl- and 8-ethoxy-1-phenylpyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrid-azines.     

An Efficient Four‐component Synthesis of Spiro[indoline‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrimidine]triones

A four‐component reaction in the presence of Alum [KAl(SO₄)₂·12H₂O] as an inexpensive and reusable catalyst using the ionic liquid as an effective green reaction media is reported.     

Green Synthesis of Spiro[indoline‐3,4′‐pyrazolo[3,4‐b][1,6]naphthyridine]‐2,5′(1′H)‐diones Catalyzed by TsOH in Ionic Liquids

A three‐component reaction of isatin, 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐amine, and piperidine‐2,4‐dione was treated in ionic liquids catalyzed by TsOH and provided an efficient and green method for the synthesis of spiro[indoline‐3,4′‐pyrazolo[3, 4‐b][1,6]naphthyridine]‐2,5′(1′H)‐dione derivatives in high yields.     

Synthesis of novel 1,4‐dihydropyrido[3′,2′:5,6]thiopyrano[4,3‐c]‐pyrazoles and 5H‐pyrido[3′,2′:5,6]thiopyrano[4,3‐d]pyrimidines as potential antiproliferative agents

The synthesis of new planar derivatives characterized by the presence of a pyridothiopyranopyrazole or pyridothiopyranopyrimidine nucleus, carrying a substituted aryl group, is reported. The novel 1,4‐dihydropyrido[3′,2′:5,6]thiopyrano[4,3‐c]pyrazole derivatives were obtained by condensation of 2,3‐dihydro‐3‐hydroxymethylenethiopyrano[2,3‐b]pyridin‐4(4H)‐ones with appropriate hydrazines. The preparation of 2‐substituted pyrido[3′,2′:5,6]thiopyrano[4,3‐d]pyrimidines was accomplished from the intermediate 2,3‐dihy‐dro‐3‐dimethylaminomethylenethiopyrano[2,3‐b]pyridin‐4(4H)‐ones by reaction with the appropriate binucleophile amidines. The antiproliferative activity of some new products was tested by an in vitro assay on human tumour cell lines (HL‐60 and HeLa), but none of them showed any significant effects in the tests performed. Accordingly, linear flow dichroism measurements indicated their inability to form a molecular complex with DNA.