Synthesis of 5H-tetrazolo[5,1-c][1,4]benzodiazepines

A three step synthesis of 5H-tetrazolo[5,1-c][1,4]benzodiazepin-11-ones 8a-d via the reaction of a substituted benzyl azide and ethyl cyanoformate is described. The derived lactams are converted to the corresponding 11-thiones 9a-d and, through the S-methylated derivatives, to the 11-amino analogs 11a-f. All of the described compounds are representatives of a novel ring system.     

Tricyclic heteroaromatic systems. 5H-1,2,4-triazolo[5,1-c][1,4]benzodiazepine

The synthesis of the new tricyclic heteroaromatic system 5H-1,2,4-triazolo[5,1-c][1,4]benzodiazepine, diazaanalogue of 5H-pyrrolo[2,1-c][1,4]benzodiazepine, which is the common feature of some antitumor antibiotics, is reported. The structure of the new tricyclic system and of some of its key intermediates is assigned by means of nuclear magnetic resonance studies.     

Tricyclic heteroaromatic systems. 5H-1,2,3-triazolo[5,1-c][1,4]benzodiazepine

The synthesis of the new tricyclic system 5H-1,2,3-triazolo[5,1-c][1,4]benzodiazepine, diaza-analogue of 5H-pyrrolo[2,1-c][1,4]benzodiazepine, which is the common feature of some antitumor antibiotics, is reported. The structure of the new tricyclic system and of some of its key intermediates is assigned by means of a ¹³C nmr study.     

Synthesis of 5H-imidazo[2,1-c]pyrrolo[1,2-a][1,4]benzodiazepine

We have synthesized 5H-imidazo[2,1-c]pyrrolo[1,2-a][1,4]benzodiazepine 1 in five steps from 1-(2-amino-methylphenyl) pyrrole 4 . Amidino derivatives 11-12 have also been prepared.     

Synthesis of 6,8-substituted derivatives of imidazo[5,1-c][1,2,4]triazines and 1,4-dihydroimidazo[5,1-c][1,2,4]triazin-4-ones

The cyclization of imidazolylhydrazines, synthesized from 5-diazoimidazoles and cyanoacetic acid derivatives, to 4-aminoimidazo[5,1-c][1,2,4]triazines and imidazo[5,1-c][1,2,4]triazin-4-ones has been studied. It was established that electron-withdrawing substituents at position 4 of the imidazole ring had a weak effect on the cyclization process. On the other hand, electron-donating substituents at positions 4 or 2 of this ring inhibited and in some cases completely prevented the formation of bicyclic products.Urals State Technical University (UPI), Ekaterinburg 620002, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 805–815, June, 1998.     

Synthesis of 3-tert-Butyl-4-hydroxy-1,4-dihydropyrazolo[5,1-c][1,2,4]triazines

Russian Journal of Organic Chemistry - Two new approaches have been proposed for the synthesis of 4-hydroxy-1,4-dihydropyrazolo[5,1-c]-[1,2,4]triazines via (1) borohydride reduction of...     

The synthesis of 4H-imidazo[5,1-c][1,4]benzothiazine derivatives

A facile synthesis of the 4H-imidazo[5,1-c][1,4]benzothiazine ring system is described. The synthesis utilized the annulation of an imidazole ring onto a 2H-1,4-benzothiazin-3(4H)-one via the addition of the anion of ethyl isocyanoacetate. Methods for the functionalization of the 1-, 3-, 4-, and 5-positions of the ring system are presented.     

Synthesis of 5H-10,11-dihydropyrazolo[5,1-c]-[1,4]benzodiazepinederivatives. II

Ethyl 3(5)-formylpyrazole-5(3)-carboxylate, 2-nitrobenzyl bromide or 2-nitrobenzoyl chloride are the starting basic materials to prepare with a few reaction steps, pyrazolo[5,1-c][1,4]benzodiazepines bearing at position 2 a substituted propionic chain ( 7–9 ) or bearing at position 5 a carbonyl group ( 12 ). Compounds 7–9, 12 are to be considered aza analogs of the antitumor antibiotic antramycin.     

Synthesis of new halo-substituted pyrazolo[5,1-c][1,2,4]triazines

Ethyl 3-tert-butyl-4-oxo-7-X-4,6-dihydropyrazolo[5,1-c][1,2,4]triazine-8-carboxylates (X = H, Cl, Br) were synthesized for the first time by diazotization of 7-amino-3-tert-butyl-4oxo-8-ethoxycarbonyl-6H-pyrazolo[5,1-c][1,2,4]triazines with tert-butyl nitrite in the presence of trimethylsilyl halides. A new method was developed: a reaction between 7-amino-3-tert-butyl-4-oxo-6H-pyrazolo[5,1-c][1,2,4]triazine-8-carboxylic acid and I₂/TEA followed by treatment with NaBH₄ led to a mild decarboxylation. The acid reacts with N-halosuccinimides to give novel 8-halo-substituted derivatives. The amino groups of the latter were acylated by treatment with trifluoroacetic anhydride to give monoacylation products.

     

Synthesis of 1,4-dihydroimidazo[5,1-c]-1,2,4-triazin-4-ones and imidazo[5,1-c]-1,2,4-triazoles

Azo compounds obtained by the coupling of 5-diazoimidazoles with diethyl esters of nitro-, chloro-, bromo-, and acetylaminomalonic acids under conditions of base catalysis are cyclized to give 1,4-dihydroimidazo[5,1-c]-1,2,4-triazin-4-ones or imidazo[5,1-c]-1,2,4-triazoles. The chloro, bromo, and nitro groups in the bicyclic products are readily replaced by action of nucleophiles. The imidazotriazinones are converted to chloroimidazotriazines by reaction with thionyl chloride or phosphorus oxychlorideUrals State Technical University-UPI, 620002 Yekaterinburg, Russia Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1544–1553, November, 1999.     

Synthesis of 1H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazines, 8H-pyrazolo[3,4-e]tetrazolo[5,1-c]-as-triazine and 1,7-dihydro-8H-pyrazolo[3,4-e]-as-triazine derivatives

3-Hydrazino-7-methyl-5-phenyl-5H-pyrazolo[3,4-c]-as-triazine 1 underwent ring closure and/or condensation reaction with formic acid, acetic acid, acetic anhydride and benzoyl chloride to afford 1H-pyrazolo-[3,4-d]-s-triazolo[3,4-c]-as-triazines 2, 5 and 7a and/or N-acyl derivatives 3, 4 and 6 . N-Acyl derivatives 3 and 6 underwent cyclisation reaction on treatment with phosphoryl chloride to give 5 and 7a . 3-Methyl-1-phenyl-8-aryl-1H-pyrazolo[3,4-e]-s-triazolo[34,-c]-as-triazines 7 were also prepared by the reaction of the hydrazono derivatives 8 wit thionyl chloride. On treatment of 1 with nitrous acid gave the 8H-pyrazolo[3,4-e]tetrazolo-[5,1-c]-as-triazine 9 . Compound 1 underwent ring closure with carbon disulphide or ethyl chloroformate to 1,7-dihydro-8H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazine derivatives 10 and 12 . Reaction of 1 with ethyl acetoacetate or acetylacetone gave 3-pyrazolo derivatives 13 and 14 .     

Research on nitrogen containing heterocyclic compounds. XX. Synthesis of 8H-Imidazo[5,1-c]pyrrolo[1,2-a][1,4]benzodiazepine and its 6-derivatives

Starting from 1H-1-(2-aminomethylphenyl)pyrrole the synthesis of 8H-imidazo[5,1-c]pyrrolo[1,2-a][1,4]ben-zodiazepine, a novel nitrogen containing tetracyclic ring, has been performed by two routes involving a three-step and a six-step sequence, respectively. The more complex sequence offers the advantage to obtain also 3-alkyl and 3-aryl derivatives of the parent nucleus. The three step sequence involves the use of toluene-4-sulfonylmethylisocyanide (TosMIC) as a synthon.     

Synthesis of 7-amino-3-tert-butyl-8-R-1,4-dihydro-pyrazolo[5,1-c][1,2,4]triazin-4-ones

Russian Journal of Organic Chemistry -     

Derivatives of imidazo[5,1-c][1,4]benzoxazin-l-ones and related analogs. Part I

The bicyclic 2,3,3a,4-tetrahydro-1H-imidazo[5,1-c][1,4]benzoxazin-1-one system and the related 1,4-benzo-thiazine and 4,1]benzoxazepine analogs were synthesized. They were easily obtained by melting a suitable diamine derivative with urea. Some of them displayed very good reversible MAO-I activity selective for type A. The preparation of the intermediate amines is also given.     

Synthesis of 1H- and 2H-pyrazolo[3,4-c][2,1]benzothiazepines

Starting from ethyl chlorosulfonylpyrazole-4-carboxylates we have carried out the synthesis of ketones 3 and 4 which are the first two structures of the novel 1H- and 2H-pyrazolo[3,4-c][2,1]benzothiazepine ring systems.     

Synthesis of novel imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines

Several 1 1-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines have been used as starting material to prepare a number of derivatives of 9H-imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and 10H-pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines. The imidazole nucleus was built by reaction of amidines with ethyl bromopyruvate or aminoacetaldehyde dimethylacetal. Several derivatives of imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine have been prepared by formylation of the pyrrole ring followed by formation of thioamides. Condensation of 11-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines with diethyl ethoxymethylenemalonate afforded intermediate diesters which were transformed into the corresponding 10H-pyrimido[1,2-a]pyrrolo[2,1-c]-benzodiazepines.     

Synthesis of Sequence-Selective C8-Linked Pyrrolo[2,1-c][1,4]benzodiazepine DNA Interstrand Cross-Linking Agents

An efficient convergent synthesis of a homologous series of C8-linked pyrrolobenzodiazepine dimers with remarkable DNA interstrand cross-linking activity and potent in vitro cytotoxicity is reported. The "amino thioacetal" cyclization procedure was used to produce the electrophilic DNA-interactive N10-C11 imine moiety during the final synthetic step. In order to construct the key A-ring fragments (9a-d), a versatile convergent approach has been developed to join two units of vanillic acid with alpha,omega-dihaloalkanes of varying length to provide the required bis(4-carboxy-2-methoxyphenoxy)alkanes while avoiding the formation of mixtures of monoalkylated and bisalkylated products.     

Pyrrolo[1,4]benzodiazepines. III. synthesis of 5,11-dioxo-1,10,11,11a-tetrahydro-2-vinyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine

Some pyrrolo[2,1-c][1,4]benzodiazepines having a chain of two carbon atoms, as it is found in antibiotic tomaymycin, were prepared. The first reaction was the C-acetylation of 1-(2-nitrobenzoyl)-Δ⁴-pyrroline-2,2-dicarboxylic acid diethyl ester; successive transformations of the acetyl group and cyclization gave the proposed structures.     

Synthesis of some hydroxy and methoxymethyl derivations of 1H-pyrazolo[5,1-c]-1,2,4-triazoles

Electrophilic hydroxylation of a pyrazolotriazole with a mixture of trifuoroacetic attack of methanolic hydroxide ion on a dichloropyrazolotriazole gave a 6-methoxymethylpyrazolotriazole by a mechanism involveing a cyclopropane intermediate.