Synthesis of 1,2-diazepino[3,4-b]quinoxalines and pyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4-b]quinoxalines via a 1,3-dipolar cycloaddition reaction

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 8 with furfural, 3-methyl-2-thiophene-carbaldehyde, 2-pyrrolecarbaldehyde, 4-pyridinecarbaldehyde and pyridoxal hydrochloride gave 6-chloro-2-[2-(2-furylmethylene)-1-methylhydrazino]quinoxaline 4-oxide 5a , 6-chloro-2-[1-methyl-2-(3-methyl-2-thienyl-methylene)hydrazino]quinoxaline 4-oxide 5b , 6-chloro-2-[1-methyl-2-(2-pyrrolylmethylene)hydrazino]quinoxa-line 4-oxide 5c , 6-chloro-2-[1-methyl-2-(4-pyridylmethylene)hydrazino]quinoxaline 4-oxide 5d and 6-chloro-2-[2-(3-hydroxy-5-hydroxymethyl-2-methyl-4-pyridylmethylene)-1-methylhydrazino]quinoxalme 4-oxide 5e , respectively. The reaction of compound 5a or 5b with 2-chloroacrylonitrile afforded 8-chloro-3-(2-furyl)-4-hydroxy-1-methyl-2,3-dihydro-1H-1,2-diazepino[3,4-b]quinoxaline-5-carbonitrile 6a or 8-chloro-4-hydroxy-1-methyl-3-(3-methyl-2-thienyl)-2,3-dihydro-1H-1,2-diazepino[3,4-b]quinoxaline-5-carbonitrile 6b , respectively, while the reaction of compound 5e with 2-chloroacrylonitrile furnished 11-chloro-7,13-dihydro-4-hydroxy-methyl-5,14-methano-1,7-dimethyl-16-oxopyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4-b]quinoxaline 7.     

CHEMICAL BEHAVIOR OF SOME BENZ[b] INDENO[1,2-e] [1,4] THIAZINE DERIVATIVES

Abstract

The study of the chemical behavior of some benz[b] indeno[1,2-e] [1,4] thiazine derivatives was accomplished. Different reactivities were observed for 4b,5-dihydrobenz[b]-indeno[1,2-e] [1,4] thiazine-10α(11H)-ol (3) and 5-ethyl-4b,5-dihydrobenz[b] indeno[1,2-e]-[1,4] thiazine-10α(11H)-ol (5); 3 is reoxidated to benz[b] indeno[1,2-e] [1,4] thiazine-10α(11H)-ol (2), while 5 undergoes transposition and oxidation to spiro[3-ethylbenzo-thiazol-2(3H), 1′-indan-2′-one] (6). Possible pathways for these transformations are discussed.     

Synthesis of 1,3,4,14b-tetrahydro-2H,10H-pyrazino[1,2-α]- pyrrolo[2,1-c][1,4]benzodiazepines

1,3,4,14b-Tetrahydro-2H,10H-pyrazino[1,2-α]pyrrolo[2,1-c] [1,4]benzodiazepines (1a-e) were synthesized to investigate their potential CNS activity. The key step in the synthesis was the formation of the 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (13) by reduction and concomitant cyclization of the nitroketone (11). Biological evaluation of 1a-e revealed interesting properties for 1b (CGS 7525A) [2].     

Determination of midazolam and its major hydroxy metabolite in plasma by gas liquid chromatography. Application to a pharmacokinetic study

A sensitive gas liquid chromatographic (GLC) assay was developed for plasma determinations of 8-chloro-6-(2′ -fluorophenyl)-1-methyl-4H-imidazo[1,5 α][1,4]benzodiazepine (compound I) and its hydroxymethylimidazo metabolite (compound II). The internal standards used were 8-chloro-6-(2′ -chlorophenyl)-1 -methyl-4H-imidazo[1,5 α][1,4]benzodiazepine (compound VI) and 7-chloro-5-(2′ -fluorophenyl)-1, 3-dihydro-1-(hydroxyethyl)-2H-1,4-benzodiazepin-2-one (compound VII) for compounds I and II, respectively. Following extraction, and silylation for compound II, compounds I and II were analyzed by GLC using a glass column packed with 5% OV-101 on Gas-Chrom Q, and a ⁶³Ni electron-capture detector. The GLC method was validated by a CI-GC/MS technique. The detection limit of the assay is approximately 4–5 ng/ml for compound I and 3 ng/ml for compound II. The method was used in comparative pharmacokinetic studies of the distribution of the two compounds in arterial and venous blood.     

Novel heterocycles. Synthesis of 2,3-dihydro-6-methyl-2-phenyl-4H,6H-pyrano[3,2-c][2,1]benzothiazin-4-one 5,5-dioxide and related compounds

The reaction of 2-chloro-4-(methylsulfonyl)benzoyl chloride ( 5 ) with 1-methyl-1H-2,1-benzothiazin-4-(3H)-one 2,2-dioxide ( 4 ) gave the O-benzoyl compound, 1-methyl-2,2-dioxido-1H-2,1-benzothiazin-4-yl 2-chloro-4-(methylsulfonyl)benzoate ( 6 ), which rearranged to give the C-benzoyl isomer, [2-chloro-4-(methylsulfonyl)phenyl] (4-hydroxy-1-mefhyl-2,2-dioxido-1H-2,1-benzothiazin-3-yl)methanone ( 7 ). The O-cinnamoyl compound 13 that resulted from the addition of 2,4-dichlorocinnamoyl chloride ( 11 ) to compound 4 rearranged to give the C-cinnamoyl compound, 3-(2,4-dichlorophenyl)-1-(4-hydroxy-1-methyl-2,2-dioxido-1H-2,1-benzothiazin-3yl)-2-propen-1-one ( 15 ). On the other hand, 1-methyl-2,2-dioxido-1H-2,1-benzothiazin-4-yl 3-phenyl-2-propenoate ( 19 ) (from cinnamoyl chloride ( 17 ) and compound 4 ) rearranged to give 2,3-dihydro-6-methyl-2-phenyl-4H,6H-pyrano[3,2-c][2,1]benzothiazin-4-one 5,5-dioxide ( 21 ), an example of a hitherto unknown ring system. Additional examples of this novel heterocycle were prepared from 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 23 ) and 1-methyl-1H-thieno[3,2-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 8 ).     

A convenient synthesis of novel pyridazino[3,4-b]quinoxaline and pyrazolo[3,4-b]quinoxaline utilizing 1,3-dipolar cycloaddition reaction

The reaction of 2,6-dichloroquinoxaline 4-oxide 4 with methylhydrazine gave 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 5, whose reaction with dimethyl acetylenedicarboxylate or 2-chloroacrylonitrile resulted in the 1,3-dipolar cycloaddition reaction to afford 7-chloro-3,4-bismethoxycarbonyl-1-methyl-1,2-dihydropyridazino[3,4-b]quinoxaline 6 or 6-chloro-3-hydroxymethylene-1-methyl-2,3-dihydro-1H-pyrazolo[3,4-b] quinoxaline hydrochloride 7, respectively.     

A reinvestigation of the synthesis of 3H-[1,2]diazepino[5,6-b]indoles. The synthesis of pyrido[4,3-b]indoles

Recently reported [1] syntheses of 6-methyl-1,2,4,5-tetrahydro-1,4-dioxo-3H[1,2]diazepino[5,6-b]indole ( 5 ) and 4-hydroxy-6-methyl-3H[1,2]diazepino[5,6-b]indole ( 12 ) were reinvestigated and shown to be in error. The correct assignments for these respective structures are 3-amino-1,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2,4(3H)-dione ( 6 ) and 3-amino-3,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2-one ( 13 ). Condensation of 6 and 13 with p-nitrobenzaldehyde produced benzylidene derivatives, which confirmed the presence of the amino groups.     

A new method for the synthesis of novel 1-aryl-3-heteroaryl-1H-pyrazolo[3,4-b]quinoxalines

The reaction of 3-(2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxaline 4 with o-chlorobenzenediazonium chloride gave 3-[α-(o-chlorophenylhydrazono)-2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-ylmethyl]-2-oxo-1,2-dihydroquinoxaline 6 , whose refluxing in phosphoryl chloride/pyridine afforded 1-(o-chlorophenyl)-3-(2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-yl)-1H-pyrazolo[3,4-b]quinoxaline 7. The reactions of 6 and 7 with nitrous acid resulted in sulfur extrusion to provide 1-(o-chlorophenyl)-3-(4-methyl-4H-1,2,4-triazol-5-yl)1H-pyrazolo[3,4-b]quinoxaline 8 and 3-[α-(o-chlorophenylhydrazono)-4-methyl-4H-1,2,4-triazol-5-ylraethyl]-2-oxo-1,2-dihydroquinoxaline 9 , respectively.     

Synthesis of a novel pyrrolo[1,2-c][1.3]benzodiazepine analogue of VPA-985

The seven-step synthesis of a novel structural isomer of VPA-985, N-[3-chloro-4-(5H-pyrrolo[1,2-c][1.3]benzodiazepin-6(11H)-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide, is described. (2-Aminophenyl)(1H-pyrrol-2-yl)methanone was converted with thiophosgene into (2-isothiocyanatophenyl)(1H-pyrrol-2-yl)methanone which was cyclised in the presence of base to 5-thioxo-5,6-dihydro-11H-pyrrolo[1,2-c][1.3]benzodiazepin-11-one. The latter underwent desulfurisation with Raney nickel followed by reduction with lithium aluminium hydride in the presence of aluminium trichloride and the resulting 6,11-dihydro-5H-pyrrolo[1,2-c][1.3]-benzodiazepine acylated with 2-chloro-4-nitrobenzoyl chloride to afford 6-(2-chloro-4-nitrobenzoyl)-6,11-dihydro-5H-pyrrolo[1,2-c][1.3]benzodiazepine. The nitro group in the latter compound was reduced with zinc and ammonium chloride to give the corresponding aniline derivative which was then acylated with 2-methyl-5-fluorobenzoyl chloride to provide the final product.     

Synthesis of 4H-1,3,4-oxadiazino[5,6-b]quinoxalines from 2-substituted quinoxaline 4-oxides

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 8 with acetic anhydride resulted in the intramolecular cyclization to give 8-chloro-2,4-dimethyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline 7a , while the reaction of compound 8 with acetic anhydride/pyridine or acetic anhydride/acetic acid afforded 3-(2,2-diacetyl-1-memymydrazmo)-7-chloro-2-oxo-1,2-dihydroquinoxaline 9 , effecting no intramolecular cyclization. The reaction of 2-(2-acetyl-1-methylhydrazino)-6-chloroquinoxaline 4-oxide 10a or 6-chloro-2-(1-methyl-2-trifluoroacetylhydrazino)quinoxaline 4-oxide 10b with phosphoryl chloride provided compound 7a or 8-chloro-4-memyl-2-trifluoromethyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline 7b , respectively. The reaction of compound 7b with phosphorus pentasulfide gave 7-chloro-3-(1-methyl-2-trifluoroacetylhydrazino)-2-thioxo-1,2-dihydroquinoxaline 11 , whose dehydration with sulfuric acid in acetic acid afforded 8-chloro-4-methyl-2-trifluoromemyl-4H-1,3,4-thiadiazino[5,6-b]quinoxaline 12 .     

The synthesis of 5,10-dihydro- and 2,3,5,10-tetrahydrothiazolo-[3,2-b] [2,4]benzodiazepines, 1,2,3,4,7,12-hexahydrobenzothiazolo-[3,2-b] [2,4] benzodiazepine,and 9,14-dihydro-6H-[1]benzothiopyrano-[4′,3′:4,5]thiazolo[3,2-b] [2,4] benzodiazepine via 1,2,4,5-Tetrahydro-3H-2,4-benzodiazepine-3-thione

Catalytic reductive scission of phthalazine (II) utilizing a two-stage palladium-Raney nickel procedure afforded o-xylene-α,α′-diamine (III) in 97% yield. Treatment of III with carbon disulfide gave [o-(aminomethyl)benzyl]dithiocarbamic acid (IV), which upon thermal cyclization furnished 1,2,4,5-tetrahydro-3H-2,4-benzodiazepine-3-thione (V). Reaction of V with 1,2-dibromoethane, chloro-2-propanone, ethyl 2-chloroacetoacetate, ethyl chloroacetate, and ethyl 2-bromohexanoate gave 2,3,5,10-tetrahydrothiazolo[3,2-b][2,4]benzodiazepine (VII) and substituted 5,10-dihydrothiazolo[3,2-b][2,4]benzodiazepines (Villa and b, IX, and X), respectively. Condensation of V with 2-chlorocyclohexanone and 3-bromothiochroman-4-one afforded 1,2,3,4,7,12-hexahydrobenzothiazolo[3,2-b][2,4]benzodiazepine (XII) and 9,14-dihydro-6H-[1]benzothiopyrano[4′,3′:4,5]thiazolo[3,2-b][2,4]benzodiazepine(XIll). None of the compounds possessed appreciable biological activity.     

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.     

5,6-Dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4,4-diacetic acid diethyl ester,an useful synthon for the synthesis of new polycyclic nitrogen systems of pharmacological interest

This report describes the synthesis of derivatives of two nitrogen tetracyclic ring systems, respectively 9H,11H-pyrimido[4,3-c]pyrrolo[1,2-a][1,4]benzodiazepine and spiro[piperidine-4,4′-[4H]pyrrolo[1,2-a][1,4]-benzodiazepine], by the use of the diethyl ester of 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4,4-diacetic acid as a synthon. This compound was obtained by condensation of 1-(2-aminomethylphenyl)-1H-pyrrole with diethyl 1,3-acetonedicarboxylate in acid medium. Pyrimidopyrrolobenzodiazepine derivatives were obtained by treating either the pyrrolobenzodiazepine 4,4-diacetate or the related 4-methyl-4-acetate with phenylisocyanate in boiling diethyl ether in the presence of sodium metal. The structure of 12,13-dihydro-11,13-dioxo-12-phenyl-9H,11H-pyrimido[4,3-c]pyrrolo[1,2-a][1,4]benzodiazepine, a product formed by loss of an acetate unit when 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4,4-diacetate, sodium metal and phenyl-isocyanate reacted in boiling xylene, was proved by catalytic reduction to 11,13-dioxo-12-phenyl-12,13,14,14a-tetrahydro-9H,11H-pyrimido[4,3-c]pyrrolo[1,2-a][1,4]benzodiazepine, which was synthesized by unambiguous pathway via 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4-acetate. The 2,6-dioxospiro[piperidine-4,4′-[4H]pyrrolo[1,2-a][1,4]benzodiazepine] derivatives were synthesized from the N-BOC derivative of 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4,4-diacetic acid diethyl ester, by hydrolysis followed by treatment with 2 equivalents of 1,1′-carbonyldiimidazole (CDI) and then with aniline or benzylamine. Removal of BOC from the N-phenyl-2,6-dioxopiperidine derivative was obtained by heating the related spiroderivative in toluene in the presence of p-toluenesulphonic acid. Similar reaction failed when the N-benzyl-2,6-dioxopiperidine analog was used as substrate.     

Diazepines I. A new synthesis of 6-phenyl-4H-imidazo[1,2-a] [1,4] benzodiazepines

6-Phenyl-4H-imidazo[1,2-a][1,4]benzodiazepines are obtained on reaction of 2-amino-7-chloro-5-phenyl-3H-1,4-benzodiazepine with α-bromoketones. In the cases of 3-bromo-2-butan-one and of 3-bromo-2-pentanone, 2-alkylimidazobenzodiazepine but not 1,2-dialkyl compound is the major product. A mechanism for the imidazole ring formation is presented.     

Synthesis of 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide

The reaction of methyl 2-bromo-6-(trifluoromethyl)-3-pyridinecarboxylate ( 1 ) with methanesulfonamide gave methyl 2-[(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridine-carboxylate ( 2 ). Alkylation of compound 2 with methyl iodide followed by cyclization of the resulting methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate ( 3 ) yielded 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 4 ). The reaction of compound 4 with α,2,4-trichlorotoluene, methyl bromopropionate, methyl iodide, 3-trifluoromethylphenyl isocyanate, phenyl isocyanate and 2,4-dichloro-5-(2-propynyloxy)phenyl isothiocyanate gave, respectively, 4-[(2,4-dichlorophenyl)methoxy]-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazine 2,2-dioxide ( 5 ), methyl 2-[[1-methyl-2,2-dioxido-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4-yl]oxy]propanoate ( 6 ), 1,3,3-trimethyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 7 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 8 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-phenyl-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 9 ) and N-[2,4-dichloro-5-(2-propynyloxy)phenyl]-4-hydroxy-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2] thiazine-3-carboxamide 2,2-dioxide ( 10 ).     

Furo[3,2-e]pyrrolo[1,2-α][1,4]diazepine and derivatives

The 5,10-dihydro-4H-furo[3,2-e]pyrrolo[1,2-α][1,4]diazepin-5-one ( 7 ) and furo[3,2-e]pyrrolo[1,2-α][1,4]diaze-pine ( 10 ) are synthesized from suitable isocyanates 3a,b in acetic acid. The reactivity of 10 (C- and N-alkyla-tion) is investigated.     

Reaction of sulfene and dichloroketene with N,N-disubstituted 5-aminomethylene-1,5,6,7-tetrahydro-2-methyl-1-phenylindol-4-ones. Synthesis of 1,2-oxathiino[6,5-E] indole and of pyrano[2,3-e] indole derivatives

The 1,4-cycloaddition of sulfene to N,N-disubstituted 5-aminomethylene-1,5,6,7-tetrahydro-2-methyl-1-phenylindol-4-ones afforded N,N-disubstituted 3,4,5,6-tetrahydro-8-methyl-7-phenyl-7H-1,2-oxathiino[6,5-e]indol-4-amine 2,2-dioxides only in the case of aliphatic N-substitution. The 1,4-cycloaddition of dichloroketene occurred normally only in the case of 1,5,6,7-tetrahydro-2-methyl-1-phenyl-5-piperidinomethyleneindol-4-one to give 3,3-dichloro-3,4,5,6-tetrahydro-8-methyl-7-phenyl-4-piperidino-7H-pyrano[2,3-e]indol-4-one. Attempted recrystallisation, dehydro-chlorination or treatment with palladium on carbon of this adduct, as well as reaction of similar enaminoketones with dichloroketene, gave instead the same product, namely 3-chloro-8-methyl-7-phenyl-7H-pyrano[2,3-e]indol-4-one, as a result of dehydrochlorination, dehydrogenation and subsequent hydrogenolysis of the C-NR₂ bond in the primary adduct.     

Synthesis, 1H- and 13C-NMR spectra,crystal structure and ring openings of 1-methyl-6,9-epoxy-9-aryl-5,6,9,10-tetrahydro-1H-imidazo [3,2-e] [2H-1,5] oxazocinium methanesulfonate

The methanesulfonic acid catalyzed reaction of 1-(4-chloro- and 2,4-dichlorophenyl)-2-(1-methyl-2-imida-zolyl)ethanones 1a and 1b with glycerol produced cis- and trans-{2-haloaryl-2-[(1-methyl-2-imidazolyl)methyl]-4-hydroxymethyl}-1,3-dioxolanes 2a and 2b with a 2:1 cis/trans ratio. Besides these five-membered ketals, the reaction of 1a with glycerol afforded a small amount of trans-{2-(4-chlorophenyl)-2-[(1-methyl-2-imidazolyl)methyl]-5-hydroxy}-1,3-dioxane ( 3a , 7%). The reaction of methanesulfonyl chloride with cis-1 formed the corresponding methanesulfonates, cis- 4 , which rapidly cyclized to the title compounds 5 . Base-catalyzed ring opening of 5 furnished 1-methyl-5,6-dihydro-6-hydroxymethyl-8-(4-chloro- and 2,4-dichlorophenyl)-1H-imidazo[3,2-d][1,4]oxazepinium methanesulfonates 7 . Acid-catalyzed hydrolyses of 5 or 7 provided 1-methyl-2-[(4-chloro- and 2,4-dichloro)phenacyl]-3-[(2,3-dihydroxy)-1-propyl]imidazolium salts 12 . Structure proofs were based on extensive ¹H and ¹³C chemical shifts and coupling constants and structures of 3a and 5a were confirmed by single crystal X-ray crystallography.     

Reactions of 6-Amino-5-Cyano-3-Methyl-1,4-Diphenyl-1H 4H-Pyrano[2,3-C]Pyrazole and its Methanimidate

Reaction of 6-amino-5-cyano-3-methyl-1,4-diphenyl- 1H,4H-pyrano[2,3-c]pyrazole 1 with triethyl orthoformate in acetic anhydride gave its methanimidate 2, which reacts with primary aliphatic and aromatic amines to give 4,6-dihydro-3-methyl-1,4-diphenyl-6- (alkyl)pyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5(lH)- imine 3 and the starting compound 1 , respectively. Treatment of 1 with o-aminophenol gave 5-(2-benzoxalyl)- 1,4-dihydro-3-methyl-1,4-diphenylpyrano[2,3-c]pyrazol- 6-amine 9.     

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.