Synthesis and reactions of tetrazolo[1,5-α]pyrimidines

The reaction of “magic malonates” (bis-2,4,6-trichlorophenyl malonates, 1 ) with 5-aminotetrazole ( 2 ) in the presence of triethylamine yields the ammonium salts 3 . Upon treatment of 3 with strong acids compounds 4a-d were obtained as a mixture of isomeric tetrazolopyrimidines ( A ) and 2-azidopyrimidines ( B ). Reaction of 4d with bromine or sulfuryl chloride leads by ring opening and decarboxylation to the halogenated tetrazole derivatives 5 or 7 , respectively. The action of acetic anhydride in pyridine on 3d yields the zwitterionic tetra-mic acid derivative 10.     

Synthesis and spectroscopic characterizations of both 4b,5-dihydro-4b-methyl-11H-isoindolo[2,1-a]benzimidazol-11-ones and 2,3,3a,4-tetrahydro-3a-methyl-1H-pyrrolo[1,2-a]benzimidazol-1-ones

The complete assignment of the ¹H and ¹³C nmr spectra of some derivatives of both 4b,5-dihydro-4b-methyl-11H-isoindolo[2,1-a]benzimidazol-11-one I and 2,3,3a,4-tetrahydro-3a-methyl-1H-pyrrolo[1,2-a]-benzimidazol-1-one II was herein reported by the combined use of one and two-dimensional nmr techniques. Eight compounds, three of which are novel, 2a, 3, 6 , were thus prepared. Their uv and ir spectra were also obtained. In addition, the mass spectra of compounds 1, 2a, 2b, 3 and 6 are reported.     

Synthesis of substituted pyrrolo[1,2-α]pyrimidines

A facile route for the synthesis of pyrrolo[ 1,2-α]pyrimidine derivatives and data for structural assignment are reported.     

Spectroscopic study of 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-α(β)-ols

3-Methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-α(β)-ols have been synthesized and studied by ir, ¹H and ¹³C nmr spectroscopy. In deuteriochloroform and perdeuteriobenzene solutions, these compounds adopt a flattened chair-chair conformation in which the cyclohexane ring is more flattened. From the ¹H and ¹³C nmr data, several stereoelectronic effects have been deduced. The complete and unambiguous assignment of all protons of the 3-azabicyclo[3.3.1]nonane system, not described up to date, has been carried out.     

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].     

9-Hydroxy-2-methyl-4H-pyrido[1,2-α] pyrimidin-4-one and its derivatives

2-Amino-3-(o-bromobenzyloxy)pyridine ( 1 ) and ethyl acetoacetate gave 9-(o-bromobenzyl-oxy)-2-methyl-4H-pyrido[1,2-α]pyrimidin-4-one ( 2 ) in 2% yield. When 1 and methyl β-amino-crotonate ( 3 ) were reacted, benzyl ether cleavage occurred and the products were 9-hydroxy-2-methyl-4H-pyrido[1,2-α]pyrimidin-4-one ( 4 ) and its ammonium salt ( 5 ). These observations led to an alternative synthesis in which 2-amino-3-pyridinol ( 6 ) and either 3 or methyl acetoacetate, ( 8 ) in diethylbenzene at 185° gave 4 in 86 and 87% yields, respectively, and the anion of 4 and o-bromobenzyl bromide gave 2 in 61% yield. Even in diethylbenzene at 185°, 1 and 8 gave only trace amounts of 2 . Thus, o-bromobenzylation of the 3-hydroxyl group in 6 markedly decreased the reactivity of the amino group in 6 toward reactions with acetoacetic esters.     

A novel synthesis of pyrido[2,3-α]indolizine

The synthesis of a new pyridoindolizine, in particular, pyrido[2,3-α]indolizine, was carried out using 2-methyl-3-t-butoxycarbonyl-4-aminopyrrole as the starting material.     

11H-isoindolo[2,1-<Emphasis Type="Italic">a</Emphasis>]benzimidazoles (Review)

Data on methods for the synthesis of isoindolo[2,1-a]benzimidazole and its derivatives and their chemical characteristics are reviewed. Data from quantum-chemical calculations of certain structures are presented. Possible practical applications of the compounds are indicated. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 323–351, March, 2007.     

Imidazo[1,2-α]pyridine anthelmintics. Synthesis of 6-phenylaminoimidazo[1,2-α]pyridine-2-carbamate and 5-acylaminopyridines by a chapman rearrangement

The title compound, a potential anthelmintic agent, was prepared in seven steps from 5-hydroxy-2-picoline. The intermediate 5-(N,-phenylbenzamido)-2-picoline was prepared by a facile Chapman rearrangement of the corresponding benzimidoyl ester. Oxidation and Curtius rearrangement of the substituted picoline gave 5-(N-phenylbenzamido)-2-aminopyridine which underwent ring closure and debenzoylation to furnish methyl 6-phenylaminoimidazo[1,2-α]pyridine-2-carbamate. Fries rearrangement of the penultimate N-benzoyl derivative gave a 6-(p-benzoylphenylamino)imidazo[1,2-α]pyridine derivative, whose structure was confirmed by cmr study. The title compound lacked significant anthelmintic activity.     

Imidazo[1,2-α]pyrimidines and 1,2,4-triazolo[1,5-α]pyrimidines: Two new examples of mesoionic xanthine analogs

Several derivatives of mesoionic imidazo[1,2-α]pyrimidine-5,7-dione and 1,2,4-triazolo[1,5-α]pyrimidine-5,7-dione, two new examples of mesoionic xanthine ring systems, were prepared and characterized. These compounds were conveniently prepared by the condensation of bis-(2,4,6-trichlorophenyl) malonates with the appropriately substituted alkylaminoimiazole or 1,2,4-triazole.     

Facile Synthesis of 3-Substituted Thiazolo[2,3-α]tetrahydroisoquinolines

It was found that 4-hydroxy-2-butenoic ester (11) could not react with 3,4-dihydro-isoquinoline (4a). Individual addition reactions of γ-mercapto-α,β-unsaturated esters (18) and -unsaturated amide (19) with 3,4-dihydroisoquinolines (4) were carried out under appropriate conditions to provide the corresponding thiazolo[2,3-α]isoquinoline derivatives with good yields (up to 87%) and significant diastereomeric selectivity. The mechanism of the crucial reaction was discussed.     

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.     

13C-NMR-Untersuchungen zur Azido-Tetrazol-Valenzisomerie. Tetrazolo[1,5-α]pyrimidine

¹³C NMR has been used to study the azido-tetrazolo valence isomerism of three tetrazolo[1,5-α]pyrimidines. Large chemical shift variations of C-4 carbons were found to be useful to distinguish between azido and tetrazolo isomers. Furthermore, the structure of new heterocycles has been proved and the report of LaNoce and Giuliani concerning 9-methyl-s-triazolo[4,3-c]tetrazolo[1,5-α]pyrimidine is shown to be incorrect.     

Some reactions of 5h-indeno[2,1-b ]pyrylium,thiopyrylium and pyridinium derivatives

The reactions of 5H-indeno[2,1-b]pyrylium, thiopyrylium and pyridinium derivatives with aldehydes and 2,6-diphenyl-4H-pyran-4-one are described. The products obtained from the pyrylium salt and piperidine as well as the Vilsmeier reagent are reported.     

Synthesis of 1,3,4-thiadiazolo[3,2-α]pyrimidin-5-one and isomeric 7-one derivatives

Continuing preceeding studies, designed to obtain derivatives of 1,3,4-thiadiazolo[3,2-α]pyrimidin-5-one and of the isomeric 7-one of pharmacological interest, some of the above mentioned compounds were prepared. Their structural identification was obtained by mass spectra.