Synthesis of Imidazo[1,2-c]pyrazolo [4,3-e]pyrimidines Derived From Indole and Related Heterocycles

Summary. The syntheses of the title heterocycles were achieved using 5-amino-1-(1-benzyl-1H-indol-3-ylcarbonyl)-1H-pyrazole-4-carbonitrile as starting material. These compounds were converted into the 4-imidazolinyl derivatives which were subjected to cyclization reactions to afford the title compounds.     

Pyrazoles and Pyrazolo[4,3- e]pyrrolo[1,2- a]pyrazines, I. Synthesis and Antimicrobial Activity

The synthesis of the title compounds was achieved using 1-phenyl-5-(pyrrol-1-yl)-1H-pyrazole-3-carboxylic acid azide as starting material. The latter compound was allowed to react with alcohols and amines to afford the corresponding carbamates and urea derivatives. Alkaline hydrolysis of the carbamates gave the corresponding amine, which was acylated and/or aroylated to give amide derivatives. These and the urea derivatives were subjected to cyclodehydration to give the title compounds. Antibacterial and antifungal activities were observed for several derivatives.     

Synthesis of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines

Starting from 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones, a synthesis pathway to the tricyclic pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines is described. Reaction of 1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-ones with phosphoryl chloride afforded the corresponding 4-chloro-1H-pyrazolo[3,4-d]pyrimidines. Treatment of these compounds with hydrazine hydrate at reflux temperature gave the hydrazino derivatives, which were subsequently cyclized to the titled compounds on heating with orthoesters in ethanol.     

Heterocyclic system. XI. Synthesis of 1H,4H-pyrazolo[4,3-b]pyrrolizine and 2H,4H-pyrazolo[4,3-b]pyrrolizine derivatives

Cyclization of pyrrolidinocarboxamide derivatives of 1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazole-4-carboxylic acid and 2-phenyl-3-(1H-pyrrol-1-yl)-1H-pyrazole-4-carboxylic acid afforded imminium salts which were transformed into the corresponding ketones. Further reduction of the latter compounds furnished the title derivatives.     

A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones

Abstract  

The reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one or its 2-methylthio derivative with hydrazonoyl halides, in the presence of triethylamine, yielded 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The structure of the latter compounds was further confirmed by reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one with the appropriate active chloromethylenes followed by coupling of the products with benzenediazonium chloride to afford the non-isolable azo-coupling products which converted, in situ, to 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The reaction mechanism was proposed and the products were screened for their biological activity. Some of the newly synthesized compounds had a moderate effect against some bacterial and fungal species.     

4-Substituted-4H-pyrrolo[2,1-c] [1,4]benzoxazines

The condensations of 1-(2-hydroxyphenyl) pyrroles with a variety of carbonyl compounds are shown to give new 4-substituted-4H-4-methylpyrrolo[2,1-c][1,4]benzoxazines. Some of the products were further functionalized. The ir, uv, and pmr spectra of the title heterocyclic system are discussed. Reaction of 1-(2-hydroxyphenyl) pyrrole with dimethyl acetylenedicarboxylate yielded dimethyl 3-(2-hydroxyanilino) phthalale; a mechanistic rationale which accounts for the result involves a rearrangement of the hypothetical Diels-Alder adduct.     

Derivatives of benzo[4,5]cyclohepta[1,2-b]thiophene 3. Synthesis of 2,3,6,7-tetrahydro-3-oxobenzo[1,2]cyclohepta[3,4,5-hi]thieno[3,4-c]pyridine and 2,3,7,8-tetrahydro-3-oxothieno[2,1-b]cyclohepta[5,6,7-de]isoquinoline

The title compounds 3 and 4 were synthesized by cyclization via isocyanate of the Z and E-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene-4-ylidenacetic acids 8 and 9 , which in turn were prepared by the Wadsworth-Emmons reaction of ketone 5 with triethyl phosphonacetate followed by separation and independent hydrolysis of the corresponding esters 6 and 7 . The structures of these new compounds as well as the configurations of their isomeric precursors are described.     

1,3-偶极环加成合成新型3a,6a-二氢-4,6-二氧代吡咯啉并[3,4-d]吡唑类衍生物

α-氯代-4-氧代-4H-1-苯并吡喃-3-甲醛芳腙与N-取代苯基-马来酰亚胺在三乙胺作用下通过1,3-偶极环加成合成了一系列含3-(4-氧代-4H-1-苯并吡喃-3-基)-3a,6a-二氢-4,6-二氧代吡咯啉并[3,4-d]吡唑类衍生物. 化合物结构经元素分析, IR, ¹H NMR及MS确证.     

Synthesis of some 5H,12H-[1]benzoxepino[4,3-b]indol-6-ones. A new heterocyclic ring system

The synthesis of the title compounds 5H,12H-[1]benzoxepino[4,3-b]indol-6-ones 10 was effected by the Fischer indole cyclization of some 2,3-dihydro-4-phenylhydrazono[1]benzoxepin-5-ones 9 , obtained from the 3,4-dihydro-4-hydroxymethylene[1]benzoxepin-5(2H)-ones 7 by the Japp-Klingemann reaction. The structure of these new heterocyclic compounds was supported by ir, ¹H nmr and ms spectral data.     

The synthesis of monomethoxy[1]benzothieno[2,3-c]quinolines

A series of monomethoxy[1]benzothieno[2,3-c]quinolines 24-28 were prepared by photocylization of the appropriate 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamides 9–13 to [1]benzothieno[2,3-c]quinolin-6(5H)-ones 14-18 followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 19-23 then dechlorination resulting in the title compounds except for 25 which was achieved by direct reduction of 15 . Reaction of 24-28 with methyl iodide provided the corresponding N-methyl quaternary salts 29-33 . Also, conversion of 4-meth-oxy[1]benzothieno[2,3-c]quinolin-6(5H)-one 16 to 4-methoxy-6-methylthio[1]benzothieno[2,3-c]quinoline 35 and 4,6-dimethoxy[1]benzothieno[2,3-c]quinoline 36 is described.     

Research on nitrogen heterocyclic compounds. XV. Synthesis of 1H,4H-pyrazolo[4,3f]pyrrolo[1,2-a][1,4]diazepine derivatives

The synthesis of derivatives of 1H,4H-pyrazolo[4,3-f]pyrrolo[1,2-a][1,4]diazepine, a new tricyclic nitrogen-containing nucleus is reported. Condensation of arylaldehydes with 4-aminomethyl-1-phenyl-5-(1-pyrryl)pyrazole afforded the title compounds. Bischler-Napieralski intramolecular cyclization of 4-acetamidomethyl-1-phenyl-5-(1-pyrryl)pyrazole was also studied. The reaction led to 6-methyl-1-phenyl-1H,4H-pyrazolo[4,3-f]pyrrolo[1,2-a][1,4]diazepine or alternatively to 4-chloromethyl-1-phenyl-5-(1-pyrryl)pyrazole depending on the solvent used.     

Die Synthese von Azaisomeren des Triesters von PQQ: 3H-Pyrrolo[3,2-f]-, 1H-Pyrrolo[3,2-h]- und 7H-Pyrrolo[2,3-h]chinolinchinon-Derivate

The Synthesis of Azaisomers of the Triester of PQQ: 3H-Pyrrolo[3,2-f]-, 1H-Pyrrolo[3,2-h]-, and 7H-Pyrrolo[2,3-h]quinolinequinone Derivatives We describe here the synthesis of the title compounds 3–5 , starting from highly substituted aminoindoles. The annelated pyridine rings were built up in each case with dimethyl 4-oxoglutaconate according to Corey's procedure. All three o-quinone derivatives 3–5 are stable compounds, comparable to PQQ-triester. The azaisomers vary in biological activity from practically inactive to strong inhibition of the α-amidating enzyme or the ornithin decarboxylase.     

Derivatives of benzo[5,6]cyclohepta[1,2-b]thiophene. Synthesis of 2,3,7,8-tetrahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline and 1,2,3,7,8,11b-hexahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline

The synthesis of the title compounds was carried out by cyclization via isocyanate of (E)-4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylideneacetic acid and 4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylacetic acid respectively, which were obtained by the Wadsworth-Emmons modification of the Wittig reaction of 4,5-dihydro-10H-10-oxobenzo[5,6]cyclohepta[1,2-b]thiophene and triethyl phosphonacetate. The structures of these new compounds are described.     

Synthesis of new imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(6H)-one derivatives by iodocyclization of 6-alkenyl(alkynyl)-aminopyrazolo[3,4-d]pyrimidin-4(5H)-ones

6-Allyl(diallyl, prop-2-yn-1-yl)amino-1-R-pyrazolo[3,4-d]pyrimidin-4(5H)-ones reacted with iodine to give angularly fused 8-iodomethyl-7,8-dihydro-1-R-imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(6H)-ones which were treated with sodium acetate to obtain 8-methylidene-1-R-7,8-dihydroimidazo[1,2-a]pyrazolo-[4,3-e]pyrimidin-4(6H)-ones as a result of elimination of hydrogen iodide. 8-Methylidene-1-R-7,8-dihydroimidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(6H)-ones were converted into 8-methyl-1-R-imidazo[1,2-a]pyrazolo-[4,3-e]pyrimidin-4(5H)-ones on heating to the melting point. 8-Methylidene-1-phenyl-7,8-dihydroimidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(6H)-one underwent isomerization into linearly fused 6-methyl-1-phenyl-1,8-dihydro-4H-imidazo[1,2-a]pyrazolo[3,4-d]pyrimidin-4-one on heating in sulfuric acid.     

A new, one-pot, three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines

A new, one-pot and three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines is described. The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by N-(2-heteroaryl)amides to yield a ketenimine intermediate, which was cyclized and then rearranged under the reaction conditions to afford the title compounds under mild reaction conditions in good yields. Single-crystal X-ray analysis conclusively confirms the structure of the obtained bridgehead bicyclic 6-6 heterocyclic compounds.     

Synthesis of 4-(2-chloroethyl)-2,3-dihydro[1,4]oxazino[2,3-b]quinoline and 4-(2-chloroethyl)2,3-dihydropyrido[2,3-b][1,4]oxazine

The title compounds were synthesized from 3-[bis(2-hydroxyethyl)amino]quinolin-2(1H)-one 11a and 3-[bis(2-hydroxyethyl)amino]pyridin-2(1H)-one 18 respectively. The preparation involved a tandem chlorination/cyclization reaction.     

On the Synthesis of Pyrrolobenzo[b]thieno[1,4]diazepines

2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile was converted into the corresponding 2-(pyrrol-1-yl) derivative, followed by reduction of the latter compound into the corresponding amine. This amine and its acyl, aroyl, and arylidene derivatives were used as synthons in the synthesis of several title compounds.     

Water-Mediated Selective Synthesis of Pyrazolo[1,5-a]quinazolin-5(4H)-ones and [1,2,4]Triazolo[1,5-a]quinazolin-5(4H)-one via Copper-Catalyzed Cascade Reactions

A convenient and sustainable synthesis of pyrazolo[1,5-a]quinazolin-5(4H)-ones and [1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one through copper-catalyzed cascade reactions of 2-bromobenzoates with 1H-pyrazol-5-amines or 1H-1,2,4-triazol-5-amine under ligand-free conditions in water is presented. It is notable that aqueous medium turned out to be crucial for the chemoselective formation of the title compounds. Compared with literature protocols, this new method showed advantages such as simple and sustainable procedure, commercially available starting materials, and convenient reuse of the reaction medium together with the copper catalyst.     

Synthesis of 1-[3-methyl-2(3H)-benzazolon-5- or 6-yl]-4-{4-[cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-yl]methyleneoxyphenyl}piperazines

Reactions of 3-methyl-6-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzoxazolone, 3-methyl-6-[4-(4-hydroxy-phenyl)-1-piperazinyl]-2(3H)-benzothiazolone and 1,3-dimethyl-5-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzimidazolone with cis-{[2-(2,4-dichlorophenyl) -2-(1H-imidazol-1-ylmethyl)]-1,3-dioxolan-4-yl}methyl meth-anesulfonate in the presence of sodium hydride furnish the title compounds.     

The synthesis of 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles,11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles and 1,2,4-triazolo[3,4-f]-1,2,4-triazino[4,5-a]indoles

This paper describes the synthesis of the previously unknown 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles (2) and 11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles (3) from 4-hydrazino-5H-pyridazino[4,5-b]indoles (1) , as well as the synthesis of 1,2,4-triazolo[3,4-f]-1,2,4-triazino-[4,5-a]indoles (10) from 2-indolecarbohydrazide (4) . Compounds 2 were obtained by acylation of compounds 1 , followed of thermal cyclization and compounds 3 by treating compounds 1 with nitrous acid. The reactions of compound 4 with formic acid or ethyl orthoformiate gave 1,2-dihydro-1-oxo-1,2,4-triazino[4,5-a]indole (6) . Treating this last compound with phosphorus oxychloride or phosphorus pentasulfide, followed by hydrazine, gave 1-hydrazino-1,2,4-triazino-[4,5-a]indole (9) . Acylation of this last compound, followed of cyclization gave compounds 10 . All the compounds were characterized by elemental analysis and ir and ¹H-nmr spectra.