Studies on the synthesis of heterocyclic compounds. Part VI. The action of methyl salicylate on some 5-aminopyrazoles

Some 1-phenyl-3-R-5-aminopyrazoles reacted with methyl salicylate to give N-(1-phenyl-3-R-pyrazol-5-yl)-2-methoxybenzamides ( 3a,b,c ), 1-phenyl-2-methyl-3-R-salicyloilimino-3-pyrazolines ( 4a,b,c ) together with 1-phenyl-3-R-5-methylamino pyrazoles ( 5a,b,c ). The structures of the new compounds 3 and 4 were determined on the basis of analytical and spectroscopic data as well as on the acid hydrolysis products.     

Reaction of N-cyanoformimidates with some heterocyclic compounds. A new synthesis of 5-azaadenine and related compounds

3-Amino-1,2,4-triazoles and 2-aminobenzimidazole were reacted with N-cyanoimidates to give 5-amino-1,2,4-triazolo[2,3-a]-1,3,5-triazines (5-azaadenines) and 4-aminobenzimidazo[1,2-a]-1,3,5-triazines, respectively. The structures of the compounds obtained were confirmed through the comparison with some of the possible isomers prepared by independant methods.     

Studies on the synthesis of heterocyclic compounds. Part V. A novel synthesis of some pyridazin-4-(1H)one derivatives and their reaction with hydrazine

Some phenylazo derivatives of β-dicarbonyl compounds 1a,b,c,d reacted with dimethylformamide dimethylacetal to yield new 1-phenyl-3-R-4-(1H)pyridazinones 3a,e and 4. When compounds 3a and 3e were treated with hydrazine hydrate, they gave rise to pyrazolo[4,3-c]pyridazines 5 and 7 , respectively. By the action of hydrazine hydrate on compound 4 , the 1-phenyl-3-(1H-pyrazol-3-yl)-4-(1H)pyridazinone 8 was obtained. The structures of all the new compounds were assigned on the basis of satisfactory analytical and spectroscopic data.     

Studies on the synthesis of heterocyclic compounds. Part X. One-step route to 1,2-dimethyl-3-R-5-salicyloylimino-3-pyrazolines

This communication outlines the development of a direct synthetic route to 1,2-dimethyl-3-R-5-salicyloyl-imino-3-pyrazolines, starting from readily available 3(5)-aminopyrazoles 1a, b, c and methyl salicylate. The structures of the new compounds 3a, b, c were determined on the basis of analytical and spectroscopic data as well as on the acid hydrolysis products.     

Studies on the synthesis of heterocyclic compounds. Part II. Action of phosphorus oxychloride on N-Methyl-N-1-phenyl-3-methylpyrazol-5-yl)-2-acetamidobenzamide

During attempts to prepare the tricyclic ring system of type III by cyclization of N-methyl-N-(1-phenyl-3-methylpyrazol-5-yl)-2-acetamido benzamide (Ib) under Bischler-Napieralski reaction conditions, the formation of the macro-heterocycle IV was observed, whose structure was determined on the basis of analytical and spectroscopic data as well as on some transformation products.     

Studies on the synthesis of chemotherapeutics. I. Synthesis of 1-(2-tetrahydrofuryl)-5-fluorouracil [ftorafur] (studies on the syntheses of heterocyclic compounds. Part 703)

Synthesis of 1-(2-tetrahydrol'uryl)-5-fluorouracil [Ftorafur] ( 1 ) which is well known as an antitumor agent from 5-fluorouracil ( 2 ) with 2-alkoxytetrahydrofurans (4) is described. Among these reactions, the best yield was obtained by using 2-t-butoxytetrahydrofuran (4h).     

Studies on the synthesis of heterocyclic compounds. Part IX. Action of N,N-dimethylformamide dimethylacetal on some oximino-β-dicarbonyl compounds

3-Oximino-2,4-pentanedione ( 1 ) and ethyl 2-oximino-3-oxobutanoate ( 6 ) reacted with N,N-dimethylformamide dimethylacetal (DFDA) to give 1,7-bisdimethylamino-3,5-dioxo-4-methoximinohepta-1,6-diene ( 4 ) and ethyl 5-dimethylamino-2-methoximino-3-oxo-4-pentenoate ( 8 ), respectively. When compounds 4 and 8 were treated with hydrazine hydrate, they gave O-methyldipyrazol-3(5)-ylketoxime ( 5 ) and ethyl 2-methoximino-3(5)-pyrazolylethanoate ( 9 ) together with its corresponding hydrazide 10 , respectively. Upon action of DFDA on 3-oximino-2,4-pentanedione ( 1 ) at -20° an explosive crystalline product was obtained. On the other hand, the reaction of 3-acetoximino-2,4-pentanedione ( 11 ) with DFDA at -20° afforded a product which in ethanol solution, spontaneously deacetylated to give 1-dimethylamino-3,5-dioxo-4-oximinohexa-1-ene ( 13 ). The structures of all the new compounds were assigned on the basis of satisfactory analytical and spectroscopic data.     

Studies on pyridazine compounds,XIX. Mesylation of 5-aminopyrazoles and related compounds

Summary Acylation of 5-amino-1-substituted pyrazoles gave — depending on the substituents in position 3 and agents used — mono-, di- and triacylated products, respectively.Poster presented at the 10^th International Congress on Heterocyclic Chemistry, Waterloo/Canada, August 11–16, 1985.     

Studies on the synthesis of heterocyclic compounds. Part IV. Further investigation of the pschorr reaction with some pyrazole derivatives

Thermal decomposition of the diazonium sulfate derived from N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-aminobenzamide afforded products formulated as 1-phenyl-3-methyl[2]benzopyrano[4,3-c]pyrazol-5-one (yield 10%), 1,4-dimethyl-3-phenylpyrazolo[3,4-c]isoquinolin-5-one (yield 10%), N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-hydroxybenzamide (yield 8%) and 4′-hydroxy-2,3′-dimethyl-1′-phenylspiro[isoindoline-1,5′-[2]-pyrazolin]-3-one (yield 20%). Decomposition of the diazonium sulfate derived from N-methyl-(1,3-diphenylpyrazol-5-yl)-2-aminobenzamide gave products formulated as 7,9-dimethyldibenzo[e,g]pyrazolo[1,5-a][1,3]-diazocin-10-(9H)one (yield 8%), 4-methyl-1,3-diphenylpyrazolo[3,4-c]isoquinolin-5-one (yield 7%) and 4′-hydroxy-2-methyl-1′,3′-diphenylspiro[isoindoline-1,5′-[2]pyrazolin]3-one (yield 10%). The spiro compounds 6a,b underwent thermal and acid-catalysed conversion into the hitherto unknown 2-benzopyrano[4,3-c]pyrazole ring system 7a,b in good yield. Analytical and spectral data are presented which supported the structures proposed.     

Studies on the syntheses of heterocyclic compounds. Part DLIV. A total synthesis of (±)-coreximine by thermolysis

Thermolysis of the dibenzyloxy-substituted benzocyclobutene IXc effected cyclization and mono-O-debenzylation to provide a facile route to the total synthesis of the protoberberine isoquinoline (±)-coreximine (XIII).     

Studies on the synthesis of heterocyclic compounds. Part I. The pschorr reaction in the pyrazole series

Preparation and structural evidence of N-methyl-(1,3-R,R'-pyrazol-5-yl)-o-nitrobenzamides (VIIIa, b) are discussed. Diazotisation of related o-aminobenzamides XIa,b followed by the Pschorr reaction afforded a very complex mixture from which pyrazolo[3,4-c]isoquinolin-5-ones XIIa.b in 7–10% yields together with N-methyl-(1,3-R,R'-pyrazol-5-yl)-o-hydroxybenzamides (XIIIa) in 15–20% yields were isolated.     

Studies in the tetraarylborates : Part VII. The preparation and reagent properties of some new nitrogen heterocyclic tetraarylboraees — especially sodium tetrakis(l-imidazolyl) borate,a novel gravimetric reagent for hydrogen ion

Three new tetraarylborates containing nitrogen heterocycles have been synthesized. Sodium tetrakis(1-imidazolyl)borate and sodium tetrakis(1-benzimidazolyl)borate were prepared in very high yield by syntheses which were easy to perform in situ. Interesting analytical properties which are very different from the carbocyclic tetraarylborates were noted in both compounds. Precipitate formation oftetrakis(1-imidazolyl)borate with hydrogen and divalent cations was observed. The feasibility of determination of the hydrogen cation by tetrakis(1-imidazolyl)borate was demonstrated.     

A new practical synthesis of 3-amino-substituted 5-aminopyrazoles and their tautomerism

It was found that 3-amino-substituted 5-aminopyrazoles could be effectively prepared via hydrolytic decarboxylation of the corresponding 3,5-diaminopyrazole-4-carboxylates under microwave irradiation. The reactions required short time (4?min) and were successfully reproduced in a larger scale and under conventional heating mimicking the microwave heating pattern. X-ray crystallography identified two different types of tautomers in crystals of related 5-aminopyrazoles with p-toluidyl and p-anisidyl moieties at the position 3, respectively.     

Studies on the syntheses of analgesics. Part XXXII. An alternative synthesis of 1,2,3,4,5,6-Hexahydro-8-hydroxy-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazoeine [Studies on the syntheses of heterocyclic compounds. Part CDLXXX]

Bischler-Napieralski reaction of the amides (VIII and IX), derived from the 3-methyl-3-pentenylamine (III) with the phenylacetic acid derivatives (V ～ VII), gave the 5,6-dihydropyridines (XII and XIII), which were reduced, followed by N-benzylation, to afford the 1,2,5,6-tetrahydropyridines (XIX ～ XXI). Grewe-type cyclization of these compounds gave 3-benzyl-3-benzazocine (II), which was already converted into pentazocine (Ic). Moreover, the 1,2,5,6-tetrahydropyridines (XIX ～ XXI) were also obtained from the 2-benzylidene-1,2,5,6-tetrahydropyridine (XVII ～ XVIII) from the N-benzylamine (IV) of III via the amides (X and XI).     

Studies on the synthesis of analgesics. Part 51. Synthesis of 4-(1-oxo-2-isoindolinyl)phenyl derivatives. [Studies on the syntheses of heterocyclic compounds. Part 779]

In order to examine their effect on carrageenin-induced edema in rats, 4-(1-oxo-2-isoindolinyl)-phenyl derivatives were synthesized. 2-Hydroxy-3-[4-(1-oxo-2-isoindolinyl)phenyl]butyramide was found to be more effective than phenylbutazone.     

Studies on the syntheses of heterocyclic compounds. Part DXCVII. A synthesis of dienone analogs by electrolytic oxidation

Electrolytic coupling reaction of laudanosine (1) gave the O-methylflavinantine (II). N-Ethoxycarbonylated dihydrostilbene (IVa) gave a rearranged dienone (Va) and N-trifluoro-acetylated dihydrostilbene (IVb) contrastively gave an unrearranged dienone (Vb).     

Aminoacids in the synthesis of heterocyclic systems. The synthesis of methyl 2-acetylamino-3-dimethylaminopropenoate and 2-(N-methyl-N-trifluoroacetyl)amino-3-dimethylaminopropenoate and their application in the synthesis of heterocyclic compounds

Methyl (Z)-2-acetylamino-3-dimethylaminopropenoate (3) was prepared from N-acetylglycine (1), which was converted with N,N-dimethylformamide and phosphorus oxychloride into 4-dimethylaminomethylene-2-methyl-5(4H)-oxazolone (2), followed by treatment with methanol in the presence of potassium carbonate, into 3. The compound 3 was shown to be a versatile reagent in the synthesis of various heterocyclic systems. With N-nucleophiles, such as heterocyclic amines 4, either methyl 2-acetylamino-3-heteroarylaminopropenoates 5 or fused pyrimidinoncs 6 were formed, dependent on the reaction conditions and/or heterocyclic substituents: C-nuclcophiles with an active or potentially active methylene group, such as 1,3-dicarbonyl compounds 7, 8 and 9, substituted phenols 10a,b, naphthols 11, 12a-c, and substituted coumarin 13a, afforded substituted pyranones 20 and 22, and fused pyranones 21, 23–26. The nitrogen containing heterocycles 14–19 produced pyranoazines 27–31 and pyranoazole 32. In all of these systems the acetylamino group is attached at position 3 of the newly formed pyranone ring. The orientation around the double bond for methyl (Z)-2-(N-methyl-N-trifluo-roacetyl)-3-dimethylaminopropenoate (36) was established by X-ray analysis.