Quinazolines and 1,4-benzodiazepines LXXIX. 8-nitro-pyrazolo[1,5-a]-[1,4] benzodiazepines

The preparation of 8-nitro substituted pyrazolobenzodiazepines from 2-fluoro-5-nitrobenzo-phenone ( 1 ) and 3,5-diacetoxymethylpyrazole ( 2 ) is reported.     

Quinazolines and 1,4-benzodiazepines. LXXXV syntheses of 3-substituted lmidazo[1,5-a] [1,4]benzodiazepines

1,4-Benzodiazepines having a leaving group in the 2-position were condensed with carbanions of 1,3-dicarbonyl compounds. The products obtained were converted to the title compounds by a sequence of steps involving hydrolytic decarboxylation, nitrosation, catalytic hydrogenation and condensation with an orthoester or an amide acetal. Oxidative condensation of the enediamine 12 with a variety of aldehydes also led to imidazo-benzodiazepines with various substituents in the 1-position.     

Quinazolines and 1,4-benzodiazepines. XCIII. Synthesis of imidazo[1,5-a][1,4]benzodiazepines from nitrooximes

The displacement of the nitro group in nitrooximes by other nucleophiles was used to prepare various 2-(hydroxyimino)methyl- and 2-(methoxyimino)methyl-1,4-benzodiazepines. These compounds were converted to imidazo[1,5-a][1,4]benzodiazepines bearing a tertiary amine, methoxy or thiomethyl group in the 3-position.     

Quinazolines and 1,4-benzodiazepines. LXXVIII Pyrazolo[1,5-a] [1,4]-benzodiazepines and Imidazo[1,5-a] [1,4]benzodiazepinones

The syntheses of novel 8-chloropyrazolo[1,5-a][1,4]benzodiazepines and of an imidazo-benzodiazepinone utilizing products from the nucleophilic substitution of fluorine in 2-fluoro-5-nitrobenzophenone ( 1 ) by pyrazole-3,5-dicarboxylic acid, dimethyl ester ( 2 ) and by 2-methyl-imidazole-4,5-dicarboxylic acid, diethyl ester ( 30 ) are described.     

Quinazolines and 1,4-benzodiazepines. XCIV. Pyrazino[1,2-a][1,4]benzodiazepines

A series of pyrazino[1,2-a][1,4]benzodiazepines were prepared by acylating the primary amino group of an α-amino-1,4-benzodiazepine-2-ylideneacetic acid ester ( 1 ) with α-chloroacyl chlorides followed by cyclo-dehydrohalogenation with triethylamine in dimethylformamide. Some pharmacological data for CNS-activity are discussed.     

Quinazolines and 1,4-benzodiazepines LVII. 1H-1,4-benzodiazepines

The preparation of the title compounds 3 and 4 using two different methods of synthesis is described. These compounds are readily reduced to 2,3-dihydro-1H-derivatives 5 . Oxidation of 2-alkylthio-1H-1,4-benzodiazepines leads to the corresponding sulfoxides and sulfones. The oxidative rearrangement of sulfones 9 to a 2H-1,4-benzodiazepin-2-one derivative 10 is also given. The “normal” addition of azodicarboxylate together with an unusual addition of two moles of acetylenedicarboxylate to the enamine double bond of 1H compounds is discussed.     

Quinazolines and 1,4-Benzodiazepines. XC. 2-Aminoimidazo[1,5-a][1,4]benzodiazepin-1-ones and derivatives

The addition of diethyl azodicarboxylate to an electron rich double bond was employed as the key step for the preparation of the title compounds. Novel tetracyclic [1,2,4]triazino[1′,6′:3,4]imidazo[1,5-a][1,4]benzodiazepines were accessible from these 2-aminoimidazo[1,5-a][1,4]benzodiazepin-1-ones.     

Synthesis of novel,substituted 4H-imidazo[1,5-a][1,4]benzodiazepines

Synthetic approaches to novel, substituted 4H-imidazo[1,5-a][1,4]benzodiazepines are described. The compounds prepared are, in general, derivatives of known ring systems and structures were assigned on the basis of spectroscopic evidence.     

Synthesis of triazolo[4,3-d], tetrazolo[1,5-a] -and quinazolino[3,2-d] [1,4] benzodiazepines

Treatment of 5-methylmercapto-1,4-benzodiazepine (I) with hydrazine hydrate gave the 5-hydrazino derivative (II, R = H) which, in turn, was conveniently cyclized to the title compounds. Another method for the synthesis of triazolo [4,3-d] [1,4] benzodiazepines (III) is also described.     

Synthesis of 5,6-dihydro-4H-pyrrolo[1, 2-a] [1,4]benzodiazepines

The title compounds are. Prepared by the reaction of carbonyl compounds with 1-(2′-amino-methylphenyl)pyrrole hydrochloride.     

Addition of dihalocarbenes to 3H-1,5-benzodiazepines. Synthesis of 2H-bisazirino[1,2-a:2′,1′-d][1,5]benzodiazepines

Addition of dihalocarbenes, generated from haloforms using a phase transfer catalyst, to 3H-1,5-benzodi-azepines gave 2H-Bisazirino[1,2-a:2′,1′-d][1,5]benzodiazepines, a new ring system.     

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.     

Quinazolines and 1,4-benzodiazepines. LXI. Syntheses of 7-Acetyl-1,4-benzodiazepines

Methods for the synthesis of the biologically active 7-acetyl-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one ( 6 ) are described. This includes two new methods for the preparation of 5-acetyl-2-aminobenzophenone ( 4 ). The crucial steps in these syntheses involve, respectively, the oxidation of an ethyl group to an acetyl group with permanganate or ceric ions ( 2 → 3; 5 → 6 ), the selective reaction of methyl lithium with the cyano group of 7-cyano-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one ( 8 ) and the efficient condensation of benzyl cyanide with the ethylene ketal of p-nitroacetophenone to form the anthranil 11 .     

Synthesis and spectral properties of substituted [1,2,4]oxadiazolo[4,5-a] [1,5] benzodiazepines

The preparation of twelve novel substituted [1,2,4]oxadiazolo[4,5-a][1,5]benzodiazepines which have potentially useful pharmacological properties; by 1.3-dipolar cycloaddition of benzonitrile oxides, generated in situ from benzohydroxamoyl chloride and triethylamine, to 1,5-benzodiazepine derivatives, is described. The structure of all products was corroborated by ir, ¹H-nmr, ¹³C-nmr and ms.     

Quinazolines and 1,4-benzodiazepines. XCV. Synthesis of 1,4-benzodiazepines by ring expansion of 2-chloromethylquinazolines with carbanions

1,4-Benzodiazepines bearing a carbon substituent at the 2-position were obtained by reaction of 2-chloromethylquinazoline 3-oxides with stabilized carbanions. The carbanions of alkyl acetates, N,N-disubstituted acetamides, acetonitrile, dimethylsulfone, N,N-dimethyl methanesulfonamide and 2-methylpyridine were successfully applied. The conversion of some of the 2-carbon substituted 1,4-benzodiazepines to imidazo[1,5-a][1,4]benzodiazepines and [1,2,5]oxadiazino[5,4-a][1,4]benzodiazepines is described.     

Synthesis of Pyrazolo[3,4-b]- and Pyrido[2,3-b]-1,5-benzodiazepines

Abstract

3-Dimethylaminomethyleno-4-phenyl-1H-1,5-benzodiazepin-2-one (1) was synthesized and reacted with hydrazines, active nitriles, and amino-heterocyclic compounds to give fused heterocyclic compounds 2–14.     

Quinazolines and 1,4-benzodiazepines XXXVI . The formation of 1,3-dihydro and 1,5-dihydro-1,4-benzodiazepines from tosyl and Mesyl - substituted 1,3,4,5-tetrahydro-5-phenyl- 1,4-benzodiazepine derivatives

The treatment of 4-sulfonyl derivatives of 5-phenyl-1,3,4,5-tetrahydro-1,4-benzodiazepin-2-ones (I) with base was shown to result in the formation of 1,3-dihydro or 1,5-dihydro-1,4-benzodiazepin-2-ones (III and II respectively) depending upon the conditions used. The base treatment of 1-sulfonyl substituted 2,3-dihydro-1,4-benzodiazepines (V) was shown to give the vinylimines VI.     

Synthesis of Substituted 5,6-Dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines

A one-pot synthetic approach to the novel 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines by thermal cyclization of 4-acylhydrazino-2,3-dihydro-1H-1,5-benzodiazepines is described.