Facile syntheses of 7,9-dimethoxypyrrolo[3,2,1-ij]quinolin-6-ones

The activated dimethoxypyrrolo[3,2,1-ij]quinolin-6-one ring system was synthesized via two approaches, starting from an indole and quinolin-4-one, respectively. Subsequent demethylation led to both monohydroxy- and dihydroxypyrrolo[3,2,1-ij]quinolin-6-ones.     

Five-membered 2,3-dioxo heterocycles: CII. Spiro heterocyclization of 3-aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones by the action of tetrahydroquinoline

3-Aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with 1,2,3,4-tetrahydroquinoline to give 3-aroyl-4-hydroxy-1-(2-hydroxyphenyl)-5′,6′-dihydrospiro[pyrrole-2,1′-pyrrolo[3,2,1-ij]quinoline]-2′,5(1H,4′H)-diones.     

Synthesis of methyl derivatives of new polycyclic systems of 4H-furo[3,2-g]pyrrolo[3,2,1-ij]quinolin-4-one,of 1H,5H- and 3H,5H-benzofuro[5,6,7-ij]quinolizin-5-one

The synthesis of new tetracyclic 4H-furo[3,2-g]pyrrolo[3,2,1-ij]quinolin-4-ones, 15–17 , 1H,5H-benzofuro[5,6, 7-ij]quinolizin-5-ones, 18–20 , and 3H,5H-benzofuro[5,6,7-ij]quinolizin-5-ones, 21–23 is described. The planarity of the structure of benzofuroquinolizin-5-one 18 was determined by X-ray single-crystal analysis.     

Synthesis of novel spiro-fused pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines

New pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines, with an associated spiro-3,3′-oxindole attachment, were prepared by three-component combinations of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1,2-dione with a pair of reactants chosen from a pyrazol-5-one, a pyrazole-5-amine, a barbituric acid, or a 6-aminouracil.     

4-hydroxy-2-quinolones. 201*. Synthesis,structure, and diuretic activity of hydroxy- and alkoxy- anilides of 6-hydroxy-2-methyl-4-oxo-2,4-dihydro- 1<Emphasis Type="Italic">H</Emphasis>-pyrrolo[3,2,1-<Emphasis Type="Italic">ij</Emphasis>]quinoline-5-carboxylic acid

Hydroxy- and alkoxyanilides of 6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids have been synthesized as potential diuretic agents. Features of their purification, their steric structure, and biological activity are discussed.     

Pyrrolo[2,3-d] pyrimidines. I. 5-hydroxypyrrolo[2,3-d] pyrimidines

5-Hydroxy-7-alkyl-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbonitriles (VIIb-d) and 5-hydroxy-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid, ethyl ester (VIIa) were prepared from 5-carbethoxy-4-chloro-2-phenylpyrimidine (IV) via 4-[(cyanomethyl)alkylamino[-2-phenyl-5-pyrimidinecarboxylic acid, ethyl esters (Vb-d) and 4-[(carboxymethyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid, diethyl ester (Va), respectively. The hydroxy group of the pyrrolo-[2,3-d]pyrimidines could be methylated, acetylated and tosylated. Hydrolysis of 5-methoxy-7-methyl-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbonitrile (IX) afforded the corresponding amide (X).     

An Efficient One-pot Synthesis of 4H-Pyrrolo[3,2,1-ij]quinolines

Summary. Dialkyl 4H-pyrrolo[3,2,1-ij]quinoline-4,5-dicarboxylates are obtained in quantitative yields from the 1:1:1 addition reaction between triphenylphosphine, dialkyl acetylenedicarboxylates, and indole-7-carboxaldehyde.     

Synthesis of new heterocyclic ring systems. Reaction of indolines and hexahydrocarbazole with α,β-unsaturated acids

Reactions of indoline (I), 2-methylindoline (II) and hexahydrocarbazole (III) with α,β-unsaturated acids in the presence of polyphosphoric acid have been investigated. Reaction of 1 with acrylic acid afforded two compounds which were identified as 1,2,4,5-tetrahydro-6H-pyrrolo-[3,2,1-ij] quinolin-6-one (IV) and 2,3,5,6,9,10-hcxahydro-1H-cyclopenta[f lpyrrolo [3,2,1-ij|-quinoline-1,8-dione (VII). The reaction oi 1 with crotonic acid gave compounds V and VIII, analogous-to IV and VII. The reaction of II with acrylic acid yielded two compounds VI and IX, whereas with crotonic acid, only X was isolated. With 111, acrylic acid afforded 5,6,8,9,10. 11,8a,11a-octahydro-4H-pyrido[3,2,1-jk]carbazol-4-one (XI) and a compound with a heretofore unknown ring system, viz., 2,3,5,6,7,8,11,12,5a,8a-decahydro-1H-cyclopenta[h] pyrido [3,2,1-jk |earbazole-1,10-dione. The structures of these compounds were deduced on the basis of their spectral and analytical data.     

7-Deazapurines II. Syntheses and reactions of 5-aminopyrrolo[2,3-d] pyrimidine-6-carbonitrile and related compounds

The reaction of 4-chloro-2-phenyl-5-pyrimidinecarbonitrile (III) with N-methylglycinonitrile gave 4-[(eyanomethyl)methylamino]-2-phenyl-5-pyrimidinecarbonitrile (VIa), which upon cycli-zation under Dieckmann conditions afforded 5-amino-7-methyl-2-phenyl-7H-pyrrolo[2,3-d]-pyrimidine-6-carbonitrile (VIIa). Other examples (VIIb and VIIc) were prepared similarly from the reactions of III with glycinamide and ethyl glycinate, respectively. The preparation of simple 5-amino derivatives of the pyrrolo[2,3-d] pyrimidines thus synthesized is described. The alkyla-tion of VIIc with N-cyeloheptylchloroacetamide took place at the ring nitrogen, giving XII. The reaction of VIIa with formamide gave 4-amino-5-methyl-7-phenyl-5H-pyrrolo[2,3-d:4,5-d′ ]-dipyrimidine (XIII), the first member of a new ring system. Treatment of VIIa with carbon disulfide and pyridine afforded another example of this new ring system, 1,5-dihydro-5-methyl-7-phenyl-2H-pyrrolo[2,3-d:4,5-d′] dipyrimidine-2,4-(3H)dithione (XIV).     

2-Amino-4-aryl-6-(ω-carboxyalkyl)-5H-pyrrolo[3,4-d]pyrimidin-7-(6H)ones. Preparation via a one-pot synthesis of 1-(ω-carboxyalkyl)-4-carbethoxy-2,3-dioxopyrrolidines

1-(ω-Carboxyalkyl)-4-carboethoxy-2,3-dioxopyrrolidines were prepared by a one-pot synthesis from β-alanine or γ-aminobutyric acid, ethyl acrylate and diethyl oxalate. In a second one-pot process these products were hydrolyzed, decarboxylated and condensed with aromatic aldehydes under the influence of hydrochloric acid to yield 1-(ω-carboxyalkyl)-4-arylidene-2,3-dioxo-pyrolidines, which yielded 2-amino-4-aryl-6-(ω-carboxyalkyl)-5H-pyrrolo[3,4-d]pyrimidin-7-(6H)-ones upon treatment with guanidine. It was shown that 3,4-dihydro derivatives of certain 2-amino-4-aryl-5H-pyrrolo[3,4-d]pyrimidin-7-(6H)ones, formed initially in the guanidine reaction, readily undergo conversion to 5H-pyrrolo[3,4-d]pyrimidin-7-(6H)ones.     

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.     

Heterocycles with a bridgehead nitrogen atom. 16. Assembly of a <Emphasis Type="Italic">peri</Emphasis>-fused system from an angular tricycle by recyclization of an oxazole ring into pyrrole one

An unusual example of the recyclization of the tricyclic 6,7,8,9-tetrahydrooxazolo[3,2-a]quinolinium system into the 8,9-dihydro-7H-pyrrolo[3,2,1-ij]quinoline system was discovered. The reaction is a topological modification of the known conversion of oxazolo[3,2-a]pyridinium salts into indolizines. The structural feature of this transformation is a change of the annelation type in the tricycle from the angular one to peri-fusion of three rings.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 253–255, January, 2005.     

Synthesis of Fluorescent Naphthoquinolizines via Intramolecular Houben–Hoesch Reaction

The repertoire of synthetic methods leading to aza‐analogues of polycyclic aromatic heterocycles has been enlarged by the discovery of the rearrangement of 10‐substituted benzo[h]quinolines into compounds bearing an azonia‐pyrene moiety. Acid‐mediated intramolecular cyclization of derivatives bearing ‐CH₂CN and ‐CH₂CO₂Et groups led to compounds bearing a 5‐substituted benzo[de]pyrido[3,2,1‐ij]quinolinium core. Advanced photophysical studies including time‐correlated single photon counting (TCSPC) and transient absorption spectroscopy of 5‐aminobenzo[de]pyrido[3,2,1‐ij]quinolin‐4‐ium salt and 5H‐benzo[de]pyrido[3,2,1‐ij]quinolin‐5‐one showed their promising optical properties such as high fluorescence quantum yields (37–59 %), which was almost independent of the solvent, and high tenability of the absorption band position upon changing the solvent. The benzo[de]pyrido[3,2,1‐ij]quinolinium salt selectively stains nucleic acids (in the nucleus and mitochondria) in eukaryotic cells.     

[3,4]-annulated pyrroles 1. Polynuclear heterocyclic systems based on pyrrolo[3,4-d]pyrimidine-2,4-dione

The intramolecular electrophilic substitution in 6-functionalized 1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-diones was used for the synthesis of pyrimido[4′,5′:3,4]-pyrrolo[1,2-a]quinoxaline-8,10(7H,9H)-dione, pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,2,4]benzo-triazine-8,10(7H,9H)-dione, and 2H-pyrimido[4′,5′:3,4]pyrrolo[1,2-a]indole-2,4,11(1H, 3H)-trione derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2180–2185, December, 2006.     

Novel heterocycles. 13 Synthesis of 5,6-dihydro-1H-3H-pyrrolo[3,2,1-ij][3,1]benzoxazine-1,3-dione

The synthesis of 5,6-dihydro-1H,3H-pyrrolo[3,2,1-ij][3,1]benzoxazine-1,3-dione ( 2a ), a new ring system, from N-acetylindoline is described.     

Synthesis of 5,6-dihydro-8-methoxy-4H-imidazo[4,5,1-ij]quinolines and some related ring systems

Reduction of amides of 8-amino-6-methoxyquinoline over platinum oxide in glacial acetic acid at room temperature affords 2-substituted-5,6-dihydro-8-methoxy-4H-imidazo [4,5,1-ij]-quinolines (I). The method could not be utilized for urea or carbamate derivatives of 8-amino-6-methoxyquinoline. 2-Amino derivatives of I were prepared through the chloro compound obtained from 5,6-dihydro-8-methoxy-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one, (IV). Several related ring systems have also been prepared.     

Application of a catalytic palladium biaryl synthesis reaction, via C-H functionalization, to the total synthesis of Amaryllidaceae alkaloids

The total synthesis of the Amaryllidaceae alkaloids dehydroanhydrolycorine, hippadine, pratosine, anhydrolycorine, assoanine, anhydrolycorin-7-one and oxoassoanine was achieved from the appropriate N-benzylisatin precursors using an intramolecular, palladium catalyzed, dehydrohalogenation, biaryl synthesis reaction to establish the carbon skeleton of the natural products. In order to avoid the formation of regioisomers in the cyclization reactions it was found necessary to incorporate the halogen on the benzyl group. Borane reduction of the 7H-pyrrolo[3,2,1-de]phenanthridine-4,5-dione derivatives gave 7H-pyrrolo[3,2,1-de]- and 4,5-dihydro-7H-pyrrolo[3,2,1-de]-phenanthridines (dehydroanhydrolycorine, dehydroassoanine, anhydrolycorine and assoanine). The former were readily reduced to the latter with NaCNBH₃ to give anhydrolycorine and assoanine. These compounds were then oxidized to anhydrolycorin-7-one and oxoassoanine whilst the same mixtures of borane reduction products could be oxidized to give hippadine and pratosine.     

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 ).     

Synthesis of 7H-tetrazolo[1,5-c]pyrrolo[3,2-e]pyrimidines and their reductive ring cleavage to 4-aminopyrrolo[2,3-d]pyrimidines

Some new 7,9-disubstituted 7H-1,2,3,4-tetrazolo[1,5-c]pyrrolo[3,2-e]pyrimidines 5 have been synthesized either by diazotization of 4-hydrazino-5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidines 4 obtained by hydrazinolysis of 4-chloro-5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidines 3 or via a substitution reaction between 3 and sodium azide. 5,7-Disubstituted-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-ones 2 were obtained by cyclocondensation of 2-amino-3-cyano-1,4-disubstituted pyrroles 1 with formic acid which on chlorination using phosphorus oxychloride afforded 3 . A novel route for the synthesis of 4-amino-5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidines 6 by the reductive ring cleavage of 5 has been reported.     

4-Hydroxy-2-quinolones. 194*. 1-Hydroxy-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-<Emphasis Type="Italic">ij</Emphasis>]quinoline-2-carboxylic acid alkylamides. Synthesis,structure, and biological properties

Modified methods are proposed for the preparation of the ethyl ester and alkylamides of 1-hydroxy-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid. A comparative analysis has been carried out of the steric structure and diuretic activity of the synthesized compounds and the previously studied, and closely structurally related, 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo-[3,2,1-ij]quinoline-2-carboxamides.