Synthesis of new functionally substituted hetarylcarbamates from methyl {4-[(2<Emphasis Type="Italic">E</Emphasis>)-3-(4-methoxyphenyl)-prop-2-enoyl]phenyl}carbamate

Three-component condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}- carbamate with ninhydrin and L-proline in methanol–water (10: 1) afforded methyl {4-[1,3-dioxo-1′- (4-methoxyphenyl)-1,1′,2′,3,5′,6′,7′,7a′-octahydrospiro[indene-2,3′-pyrrolizin]-2′-ylcarbonyl]phenyl}carbamate. Heating of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}carbamate with isatin and benzylamine in methanol gave methyl {4-[4′-(4-methoxyphenyl)-2-oxo-5′-phenyl-1,2-dihydrospiro[indole-3,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate. The condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2- enoyl]phenyl}carbamate with sarcosine and 11H-indeno[1,2-b]quinoxalin-11-one generated in situ from ninhydrin and o-phenylenediamine in boiling ethanol led to the formation of methyl {4-[4′-(4-methoxyphenyl)-1′-methyl-11,11a-dihydro-5aH-spiro[benzo[b]phenazine-6,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate.     

Five-membered 2,3-dioxoheterocycles: XCVI. Reactions of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5h)-triones with substituted 1,3,3-trimethyl-2-azaspiro[4.5]dec-1-enes

3-Aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones react with 1,3,3,7,9-pentamethyl-2-azaspiro-[4.5] deca-1,6,9-trien-8-one and 2′,5′,5′-trimethyl-4′,5′-dihydro-4H-spiro[naphthalene-1,3′-pyrrol]-4-one providing 3-aroyl-2-hydroxy-3a-{(3,3,7,9-tetramethyl-8-oxo-2-azaspiro[4.5]deca-1,6,9-trien-1-yl)methyl}pyrrolo[1,2-a-quinoxaline-1,4(3a H,5H)-diones and 3-aroyl-2-hydroxy-3a-{(5′,5′-dimethyl-4-oxo-4′,5′-dihydro-4H-spiro[naphthalene-1,3′-pyrrol]-2′-yl)methyl}pyrrolo[1,2-a]-quinoxaline-1,4(3aH,5H)-diones.     

Reactivity of 7-amino-3-tert-butyl-4-oxo-4,6-dihydropyrazolo[5,1-c][1,2,4]triazine-8-carbonitrile

By reaction of carbonyl compounds with 7-amino-3-tert-butyl-4-oxo-4,6-dihydropyrazolo[5,1-c]-[1,2,4]triazine-8-carbonitrile 3-tert-butyl-8-R-4,6,9,10-tetrahydropyrimido[4′,5′:3,4]pyrazolo[5,1-c][1,2,4]-triazine-4,10-diones and (3-tert-butyl-4-oxo-8-cyano-4,6-dihydropyrazolo[5,1-c][1,2,4]triazin-7-yl)acetamide were obtained.     

Heterocyclization of 3-(R-amino)-3-methylthio-1-phenylpropenones and 5-benzoyl-6-methylthio-1,2-dihydropyridin-2-ones with 1,2- and 1,3-dinucleophilic reagents

The interaction of 3-(R-amino)-3-methylthio-1-phenylpropenones and 1-alkyl-5-benzoyl-3-ethoxy-carbonyl-6-methylthio-1,2-dihydropyridin-2-ones with N,N- and N,C-1,2- and 1,3-dinucleophiles proceeded regioselectively by [3 + 2] and [3 + 3] cyclocondensation with the formation of derivatives of pyrazole, benzimidazo[1,2-a]-pyridine, benzimidazo[1,2-a]pyrimidine, imidazo[1,2-a]pyrimidine, [1,2,4]triazolo[4,3-b]pyridazine, and 6,7-dihydro-2H-pyrazolo[3,4-b]pyridine. The regioselectivity of the reactions carried out was analyzed.     

Synthesis of azinoazole structural isomers by photocyclization

Irradiation of 2-chloro-N-(pyridin-2-yl)pyridin-3-amine and N-(2-chloropyridin-3-yl)-4,6-dimethyl-pyrimidin-2-amine in aqueous-alcoholic solution gave new azinoazole derivatives, 6-chlorodipyrido-[1,2-a:5′,4′-d]imidazole and 1,3-dimethylpyrido[3′,2′:4,5]imidazo[1,2-a]pyrimidine, respectively.     

Anthranilic acid hydrazide in the synthesis of fused polycyclic compounds with quinazoline moieties

A modified procedure was developed for the synthesis of 5,6,7,8,13,13a-hexahydrophthalazino[1,2-b]quinazoline-5,8-dione and 6-amino-5,6,6a,11-tetrahydroisoindolo[2,1-a]quinazoline-5,11-dione from o-formylbenzoic acid and anthranilic acid hydrazide. The mechanism of the transformation is suggested, some reactions were studied, and new derivatives of these compounds were synthesized. Anthranilic acid hydrazide was used in the novel synthesis of 5-substituted phthalazino[1,2-b]quinazolin-8-one derivatives. The possible reaction mechanism is discussed. 5,6,7,8-Tetrahydrophthalazino[1,2-b]quinazoline-5,8-dione and 5-phenylphthalazino[2,1-b]quinazolin-8-one were studied by X-ray diffraction.     

SYNTHESIS OF 15H-ISOQUINO[2′,3′:3,4]IMIDAZO[2,1-B]QUINAZOLINE-7,13,15-TRIONES AND 14H-ISOQUINO[2′,3′:3,4]IMIDAZO[2,1-B]BENZO[G]QUINAZOLINE-8,14,16-TRIONE AS NEW POLYCYCLIC FUSED-RING SYSTEMS

3-Thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-dione (3) and 2-sub-stituted 3-thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-diones (4a–l) were prepared from the reaction of 2-thiohydantoin (2) and 3-substituted 2-thiohydantoin (5a–l) with 2-formyl benzoic acid (1). Alkylation of 3 under an anhydrous basic conditions afforded 4a–i. The alkylation of 3 in aqueous basic solution afforded 3-(alkylmercapto)imidazo[1,5-b]isoquinoline-1,5-diones (7a,b). Reactions of the aromatic amino acids 9a,b and 12 with 7a afforded 2-(2H-1,5 dioxoimidazo[1,5-b]isoquinazolin-3-ylideneamino)benzoic acids (10a, b) and 3-(2H-1,5-dioxoimidazo[1,5-b]isoquinazolin-3-ylideneamino)2-naphthalenecarboxylic acid (13), which were then cyclyzed by heating in acetic anhydride to afford 15H-isoquino[2′,3′ :3,4] imidazo[2,1-b]quinazoline-7,13,15-triones (11a,b) and 14H-isoquino[2′,3′:3,4]imidazo[2,1-b]benzo[g]quinazoline-8,14,16-trione (14). Some of the new compounds were tested for their antitumor activities.     

Synthesis and epimerization of 10-N-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl)-(11aS)-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-dione

The reaction of the 1,2:3,4-di-O-isopropylidene-6-O-tosyl-α-d-galactopyranose 2 with (11aS)-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-dione 1, prepared from l-proline and isatoic anhydride, gave two products which were previously reported as conformational isomers. In this work, an X-ray crystallographic study showed these to be the diastereomeric pair (11aS)- and (11aR)-10-N-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl)-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-diones as a consequence of C(11a) epimerization in the benzodiazepine moiety during glycosylation under basic reaction conditions. The hydrosolubility of the deprotected products were compared with those of the analogous benzodiazepine derivatives.     

Reaction of methyl 1-bromocyclopentane- and -cyclohexanecarboxylates with zinc and 2-arylmethylideneindan-1,3-diones

Methyl 1-bromocyclopentanecarboxylate and methyl 1-bromocyclohexanecarboxylate reacted with zinc and 2-arylmethylideneindan-1,3-diones to give methyl-1-[(aryl)(1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-methyl]cyclopentane(or cyclohexane)carboxylates and 4′-aryl-2′H-spiro[cyclopentane(or cyclohexane)-1,3′-indeno[ 1,2-b]pyran]-2′,5′(4′H)-diones.     

Synthesis of structurally constrained 4-quinazolinone derivatives with a tetrahedral C-2 atom present in three rings

The reaction of 2-aminobenzamides with 2-oxocyclopentane-, 2-oxocyclohexane-, and 2-oxocycloheptaneacetic acids esters was found to give 7a,8,9,10-tetrahydrocyclopenta[2,3]pyrrolo[1,2-a]quinazoline-6,12(7H,11H)-diones, 7,7a,8,9,10,11-hexahydro-6H-indolo[1,7a-a]quinazoline-6,13(12H)-diones, and 7a,8,9,10,11,12-hexahydrocyclohepta[2,3]pyrrolo[1,2-a]quinazoline-6,14(7H,13H)-diones, respectively. The relative configuration with the cis-fused butyrolactam and cycloalkane rings was assigned to the prepared compounds on the basis of an X-ray crystallographic study.     

Some novel heterocyclic systems derived from 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-α]benzimidazole and the corresponding diamine

The preparation of 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-a]benzimidazole from 1,4-diacetamido-2,3-dinitrobenzene is described. Reaction of this compound with 2,5-dimethoxytetrahydrofuran produces 2,3-dihydro-8-nitro-7-N-pyrrolo-1H-pyrrolo[1,2-a]benzimidazole, which can be cyclised to produce two new heterocyclic ring systems, 9,10-dihydro-8H-pyrrolo[1,2-a]pyrrolo(1′,2′:1,2]imidazo[5,4-f]quinoxaline and 9,10-dihydro-8H-pyrrolo[2,1-c]pyrrolo[1′,2′:1,2]imidazo[4,5-h][1,2,4]benzotriazine. The corresponding diamine, 7,8-diamino-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazole undergoes a variety of condensation reactions to produce several new heterocyclic systems, for example, with formic acid, 1,7,8,9-tetrahydroimidazo-[4,5-e]pyrrolo[2,1-6]benzimidazole is formed and with diacetyl, 9,10-dihydro-2,3-dimethyl-8H-pyrrolo-[1′,2′:1,2]imidazo[5,4-y]quinoxaline is obtained.     

Preparation of 2-aryl and 2-aryloxymethyl imidazo[1,2-a]pyridines and related compounds

A series of substituted 2-aryl imidazo[1,2-a]pyridines has been prepared in which a variety of substituents are introduced on the 4′-position of the phenyl ring and on the 3, 5 , 6 or 7 position of the heterocyclic ring. Most examples have acetamido, bromo, cyano, or formyl substituents at the 4′-position. Analogous imidazo-[2,1-b]fhiazoles and imidazo[1,2-a]pyrimidines have also been prepared. Another series of compounds consisting of 4′-formylphenoxymethyl derivatives of imidazole, the three positional isomers of pyridine, thiazole, benzimidazole and ring-substituted imidazo[1,2-a]pyridines has been prepared. 2-(4′-Formylphenylethenyl) derivatives of imidazole and imidazo[1,2-a]pyridine were also prepared.     

Investigation of reactions of the organozinc reagents prepared from zinc and dialkyl dibromomalonates with the derivatives of 2-arylmethyleneindan-1,3-dione and 5-arylmethylene-2,2-dimethyl-1,3-dioxane-4,6-dione

Organozinc compounds prepared from dialkyl dibromomalonates and zinc react with 2-arylmethyl-eneindan-4,6-diones, 5-arylmethylene-2,2-dimethyl-1,3-dioxane-4,6-diones, as well as with 2-[4-(1,3-dioxoindan-2-ylidenemethyl)phenyl]methyleneindan-1,3-dione and 5-[4-(2,2-dimethyl-4,6-dioxo-1,3-dioxane-2-ylidenemethyl)phenyl]methylene-2,2-dimethyl-1,3-dioxane-4,6-diones to form dialkyl 3-aryl-1′3′-dioxaspiro(cyclopropane-2,2′-indan)-1,1-dicarboxylates, dimethyl 3-aryl-6,6-dimethyl-5,7-dioxa-4,8-dioxaspiro[2,5]octan-2,2-dicarboxylates, dialkyl 2-{4-[3,3-bis (alkoxycarbonyl)-1′,3′-dioxaspiro(cyclopropane-2,2′-indan)-1-yl]phenyl}-1′,3′-dioxaspiro[cyclopropane-2,2′-indan]-1,1-dicarboxylates, and dialkyl 2-{4-[2,2-bis(alkoxycarbonyl)-6,6′-dimethyl-4,8-dioxo-5,7-dioxaspiro[2,5]oct-1-yl]phenyl}-6,6-dimethyl-4,8-dioxo-5,7-dioxaspiro[2,5]octan-1,1-dicarboxylate respectively.     

Five-membered 2,3-dioxo heterocycles: LIII. Reaction of 3-Aroyl-1<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-<Emphasis Type="Italic">c</Emphasis>][1,4]benzoxazine-1,2,4-triones with substituted 1,3,3-trimethyl-3,4-dihydroisoquinolines. A new approach to 13-aza analogs of steroids

3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with substituted 1,3,3-trimethyl-3,4-dihydroisoquinolines to give the corresponding 3-aroyl-4-hydroxy-1-(2-hydroxyphenyl)-5′,5′-dimethyl-5′,6′-dihydro-1H-spiro[pyrrole-2,2′-pyrrolo[2,1-a]isoquinoline]-3′,5-diones. 7′,8′-Benzo derivatives of the latter may be regarded as 13-azagonane analogs having a spiro-fused pyrrole ring at C¹⁶.     

Iodocyclization of 6-allylamino-4,5-dihydropyrazolo[3,4-d]pyrimidines

6-Allylamino-1-R-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidines treated with iodine in the presence of potassium carbonate are converted into 6-allylamino-1-R-1H-pyrazolo[3,4-d]pyrimidines that at further reaction with iodine undergo the cyclization into 6-iodomethyl-1-R-1,6,7,8-tetrahydroimidazo [1,2-a]pyrazolo[3,4-d]-pyrimidin-5-ium iodide of a linear structure. In the absence of potassium carbonate alongside the mentioned linear products 8-iodo-methyl-1-R-1,4,5,6,7,8-hexahydroimidazo[1,2-a]pyrazolo[4,3-e] pyrimidin-9-ium iodides of an angular structure have been obtained.     

Synthesis of nitrogen-containing heterocycles on the basis of 3-(4-acetylphenyl)-1-methylquinolin-2(1<Emphasis Type="Italic">H</Emphasis>)-one

The Meerwein reaction of 1-methylquinolin-2(1H)-one with 4-acetylbenzenediazonium chloride gave 3-(4-acetylphenyl)-1-methylquinolin-2(1H)-one which was brominated to 3-[4-(2-bromoacetyl)phenyl]-1-methylquinolin-2(1H)-one. The latter reacted with pyridine, 4-methylpyridine, quinoline, benzo[f]quinoline, and triphenylphosphine to afford the corresponding quaternary salts, and its reactions with thioacetamide, thiourea, 2-aminopyridine, and 2-aminopyrimidine led to the corresponding thiazole, imidazo[1,2-a]pyridine, and imidazo[1,2-a]pyrimidine derivatives containing a 2-oxoquinoline fragment. 3-(4-{2-[2-(Arylmethylidene)-hydrazinyl]-1,3-thiazol-4-yl}phenyl)-1-methylquinolin-2(1H)-ones were obtained by condensation of 3-[4-(2-bromoacetyl)phenyl]-1-methylquinolin-2(1H)-one with thiosemicarbazide and aromatic aldehydes.     

4-Oxo-3,4-dihydroquinazolinyl- and Benzimidazolylacetonitriles in Annelation Reactions of a Haloquinoline Ring

The interaction of 4-oxo-3,4-dihydroquinazolinyl- and benzimidazolylacetonitriles with 2,6-dihalobenzaldehydes leads to 3-(2,6-dihalophenyl)-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles and 2-(1H-benzo[d]imidazol-2-yl)-3-(2,6-dihalophenyl)acrylonitriles respectively. As a result of intramolecular cyclization of these nitriles 4-halo-12-oxo-12H-quino[2,1-b]quinazoline-6-carbonitriles and 4-halobenzo[4,5]imidazo[1,2-a]quinoline-6-carbonitriles respectively are formed.     

Thermolyzed products of naphth[1,2-d]imidazo[2,1-b]-thiazole-2,3-dione

Themolysis of naphth[1,2-d]imidazo[2,1-b]thiazole-2,3-dione ( 1 ) in dimethylformamide gave an intermediate 2-isocyanatonaphtho[1,2-d]thiazole ( 2 ), which underwent [4 + 4] cyclodimerization to yield dinaphtho-[1″,2″:4,5;1′″,2′″:4′,5′]dithiazolo[3,2-a:3′,2′-e]-1,3,5,7-tetrazocine-9,19-dione ( 3 ). The possible [4 + 2] cycloadduct, 3-(2-naphtho-[1,2-d]-thiazolyl)naphtho[1′,2′:4,5]thiazolo[3,2-a]-1,3,5-triazine-2,4-dione ( 4 ), an usual dimer type of heterocyclic isocyanates was not produced. Discrimination between the two isomers was established on the basis of spectral analyses.     

Synthesis of 11-aryl-11H-indeno[1′,2′:4,5]imidazo[1,2-a]pyridines via dehydrative cyclization of aryl(2-arylimidazo[1,2-a]pyridin-3-yl)methanols

A series of 11-aryl-11H-indeno[1′,2′:4,5]imidazo[1,2-a]pyridines was obtained via AlCl₃-promoted, dehydrative cyclization of the corresponding aryl(2-arylimidazo[1,2-a]pyridin-3-yl)methanols in moderate to good yields. The synthesized compounds can be considered as conformationally restricted, privileged aza-heterocyclic scaffold bearing triarylmethane analogs.     

Synthesis of spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones,spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones and spiro[benzofuran-2,1′-isobenzofuran]-3,3′-diones via transannular reactions of eight membered ring intermediates

An auto oxidation-rearrangement product 4 was isolated from a high dilution reaction of ninhydrin with 3,4,5-trimethoxyaniline in water. A general synthesis of this compound and its derivatives 4–6 was devised by oxidation of tetrahydroindeno[1,2-b]indol-10-ones 1–3 with sodium periodate to give isoindolo[2,1-a]-indole-6,11-diones 4–6 in good yield. Compounds 4–6 can be easily transformed into spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones 8–10 , spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones 11–13 and isoindole[1,2-a:2′,1′-b]pyrimidine-5,15-diones 15, 16 in high yields. Analogous reactions were performed on 3-amino-5a, 10a-dihydroxybenzo[b]indeno[2,1-d]furan-10-one ( 17 ) to give a dibenzoxocintrione 18 , spiro-[benzofuran-2,1′-isobenzofuran]-3,3′-dione 19 and an isoindol-1-one 20 .