First synthesis of 4H-furo[3,2-f]pyrrolo[1,2-a][1,4]diazepines

The synthetic pathway leading to 4-H-furo[3,2-f]pyrrolo[1,2-a][1,4]diazepines is described in five steps starting from 2-hydroxyketones via 2-amino-3-furonitriles.     

Synthesis of 5,6-dihydro-4H-pyrrolo[1,2-a]thieno[2,3-f][1,4]diazepines

The reduction of 1-[3-(thienyl-2-carbonitrile)]pyrrole, formed by condensation of 3-aminothiophene-2-carbonitrile with 2,5-dimethoxytetrahydrofuran, gave 1-[3-(thienyl-2-aminomethyl)]pyrrole. This compound was found to be a convenient intermediate for the preparation of 4-aryl-5,6-dihydro-4H-pyrrolo[1,2-a]thieno-[2,3-f][1,4]diazepines which was accomplished by two different synthetic routes.     

Pyirolothieno[1,4]diazepines. Part IV. First synthesis of pyrrolo-[1,2-a]thieno[2,3-f][1,4]diazepine Derivatives

Treatment of 3-(2-formyl-1H-pyrrol-1-yl)-2-thiophenecarboxamide by various nucleophiles like methyl ketones, amines, alcohols, thiols or acetates led to new 5,6-dihydro-4H-pyrrolo[1,2-a]thieno-[2,3-f][1,4]diazepines.     

Diazepines. III. Synthesis of 4H-Pyrrolo[1,2-a] thieno[3,2-f] [1,4] diazepines

The synthesis of 4H-pyrrolo[1,2-a]thieno[3,2-f] [1,4]diazepines ( 8 ) is described. Phthal-imidomethylfurans 1 were treated with bromine-methanol to give the dihydrofurans 2 , which were hydrolyzed and then liydrogenated over Raney nickel or with zinc-acetic acid to afford the 1,4-diketones 5 . Condensation of 2-amino-3-benzoylthiophenes 6 with 5 gave 3-benzoyl-2-pyrrolylthiopenes 7 . The removal of the phthaloyl group from 7 with hydrazine hydrate and ring closure to the diazepine ring yielded the new heterocycles 8 .     

New access to 4-phenyl-6H-pyrrolo[1,2-a]thieno[3,2-f]-[1,4]diazepines

Pyrrolo[1,2-a]thieno[3,2-f][1,4]diazepines were obtained in an original one step synthesis by treatment of imines 1 with paraformaldehyde in refluxing ethanol. The intermediate Mannich bases were also converted into the thienooxadiazocines 12 and the diazepine N-oxide 13 .     

A novel practical synthesis of pyrrolo[1,2-a]thieno[2,3-e][1,4]diazepines

In an investigation of new heterocyclic systems, a novel way to obtain pyrrolo[1,2-a]thieno[2,3-e][1,4]diazepine 8 was effected by ring closure to the appropriate nitroaldehyde compound which was synthesized in five steps from 3-bromomethyl-2-nitrothiophene 1 .     

Synthesis of Benzofuro[3,2-e][1,4]diazepines

A synthesis of 4-N-oxides and of 3-hydroxy derivatives of 1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-ones and of 2,3-dihydro-1H-benzofuro[3,2-e][1,4]diazepines is described. Condensation of 2-acetyl- and 2-benzoyl-3-ethoxycarbonylaminobenzofurans with acrylonitrile gave derivatives of 1,2-dihydro- and of 1,2,3,4-tetrahydrobenzofuro[3,2-b]pyridine.     

Synthesis of 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine and 10,11-dihydro-5H,12H-pyrrolo[2,1-c][1,4]benzodiazocine derivatives via cyclization of 2-aminomethylpyrroles

We have synthesized pyrrolo[1,2-α][1,4]benzodiazepine 6 and pyrrolo[2,1-c][1,4]benzodiazocines 12 and 13 from the corresponding 1-arylpyrrole 1d and 1-benzylpyrroles 7a and 7b by routes involving four and five steps, respectively.     

Pyrrolothieno[1,4]diazepines. Part V. Study of their chemical reactivity and first synthesis of oxazino[4,3-c]pyrrolo[1,2-a]thieno[2,3-f] [1,4]diazepines

The study of the chemical reactivity of methyloxopyrrolothienodiazepinones led to new derivatives such as oximes, methyloximes, hydrazones and alcohols and also, according to an intramolecular cyclization, to new oxazino[4,3-c]pyrrolo[1,2-a]thieno[3,2-f][1,4]diazepines.     

Mannich reactions. Synthesis of 4,5-dihydropyrrolo[l,2-a]quinoxalines, 2,3,4,5-tetrahydro-lH-pyrrolo[l,2-a] [l,4]diazepines and 5,6-dihydro-4H-pyrrolo[ 1,2-a] [ 1,4]benzodiazepines

l-(2-Aminophenyl)pyrrole (I) and l-[2-(aminomethyl)]phenylpyrrole hydrochloride (III) undergo cyclization reactions with aldehydes and ketones to form 4,5-dihydropyrrolo[l,2-a]- quinoxalines and 5,6-dihydropyrrolo[l,2-a][l,4]benzodiazepines, respectively. It was also found that the use of the free base of compounds corresponding to III do not cyclize directly but lead instead to the intermediate Schiff bases which are subsequently cyclized to the desired benzodiazepines by treatment with hydrochloric acid.     

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.     

Novel synthesis of imidazo[4,5-e][1,4]diazepines

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1140–1141, August, 1990.     

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.     

Microwave assisted synthesis of 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones using Mn(OAc)3

2-Hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one 2a and 7-hydroxy-5H-thiazolo[3,2-a]pyrimidin-5-one 2b, were obtained in high yields under mild conditions from the cyclization reactions of bis-(2,4,6-trichlorophenyl) malonate and 2-aminobenzothiazole or 2-aminothiazole, respectively. A new class of compounds, 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones, were synthesized via the microwave assisted radical addition of compounds 2a and 2b to various alkenes using manganese(III) acetate. A preliminary acetylcholine esterase (AchE) inhibition test of compound 4e showed excellent (92%) inhibitory potential, comparable with the standard drug Donapezil®.     

Synthesis and anticonvulsant activities of 5-(2-Chlorophenyl)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepines

A group of 5-(2-chlorophenyl)-10-(substituted)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepines 7a-c were synthesized by the acid catalyzed reaction of 5-(2-chlorophenyl)-2-hydrazino-3H-pyrido[3,4-e]-[1,4]diazepine ( 6 ) with either trimethyl orthoformate, triethyl orthoacetate or triethyl orthobenzoate, respectively. 5-(2-Chlorophenyl)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepine ( 7a ) and 5-(2-chlo-rophenyl)-10-methyl-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepine ( 7b ) exhibited good anticonvulsant activity in the subcutaneous metrazol anticonvulsant screen which serves as a model for absence (petit mal) epilepsy.     

Microwave assisted synthesis and unusual coupling of some novel pyrido[3,2-f][1,4]thiazepines

3-Amino-3-thioxopropanamide (1) reacted with ethyl acetoacetate to form 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide (2), which reacted with α-haloketones 3 to produce 2,3-disubstituted-8-hydroxy-6-methyl-2H,5H-pyrido[3,2-f]-[1,4]thiazepin-5-ones 4a-c. Benzoylation of 4c led to the formation of the dibenzoate derivative 9. Compounds 4a-c could be prepared stepwise through the formation of S-alkylated derivatives 10a-c. Compounds 2, 4a-c, 9 and 10a-c were prepared using microwave as a source of heat, and gave better yields in shorter times than those achieved by traditional methods. Coupling of 4a-c with arenediazonium chlorides proceeded unusually to give the 6-hydroxy-4-methyl-2-(arylazo)thieno[2,3-b]pyridin-3(2H)-one ring contraction products 14. Structures of the newly synthesized compounds were proven by spectral and chemical methods.     

Structure determination of some 5,6-dihydropyrrolo-[1,2-a][3,1,6]benzothiadiazocines

The conformation of compounds 1 and 2 has been determined in the solid state by X-ray crystallography and in solution by nmr spectroscopy. MM2 and molecular dynamics calculations were used to determine the conformation of compound 2 in vacuo and in solution.