Synthesis and properties of oxazolo[3,2-f]xanthines

Oxazolo[3,2-f]xanthines were synthesized by the reaction of 7-acylalkyl-8-bromo-3-methyl- and -1,3-dimethylxanthines with sodium benzoate in dimethylformamide. Their alkylation with methyl iodine was studied. The reaction of oxazolo[3,2-f]xanthines with primary amines leads to the previously described imidazo[1,2-f]xanthines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 534–537, April, 1988.     

Reaction of 7-acylmethyl-8-bromo-3-methylxanthines with formamide

A method has been developed for the synthesis of imidazo[1,2-f]xanthines and oxazolo[2,3-f]xanthine by the reaction of 7-acylmethyl-8-bromoxanthines with formamide.Translated Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1133–1135, August, 1986.     

Heterocyclic derivatives of purines. 4. Reactions of thiazolo[3,2-f]xanthineS

The chemical transformations of 2- and 3-substituted thiazolo[3,2-f]xanthines with electrophilic reagents were studied, and it was established that the 2 position of the thiazole ring is active in bromination, while the para position of the aryl substituent is active in nitration. The structures of the substances obtained were established from the IR, PMR, and mass-spectral data.See [1] for Communication 3.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1267–1271, September, 1981.     

Research in the imidazole series

It was established that the reaction of 8-theophylline with α-halo ketones gives 8-acylalkylthiotheophyllines or their cyclization products-thiazolo[2,3-f]xanthine derivatives — depending on the conditions used to carry out the reaction and the structure of the halo ketones. Derivatives of two new heterocyclic systemscy-clopentathiazolo[2,3-f]purine and benzothiazolo[2,3-f]purine-were synthesized from 2-bromocyclopentadienone and cyclohexanone. The structure and the conditions for the cyclization of 8-acylalkylthiotheophyllines to three(four)-ring compounds were studied. The structure of the thiazolo[2.3-f]xanthines was proved by reductive desulfuration to 1,3,7-trialkylxanthines.     

Purines and pyrimidines and condensed systems based on them. 4. Formation of pyrido[6,1-f]xanthines in the reaction of 7-aminotheophylline with ketones

7-Aminotheophylline reacts with acetone and acetophenone in the presence of anhydrous zinc chloride, forming 1,3,6,8-tetramethyl- and 6,8-dimethyl-1,3-diphenylpyrido[6,1-f]xanthines, respectively. 9-Aminotheophylline gives an analogous reaction product with acetone. The use of acetylacetone affords 4-acetyl-1,3,6,8-tetramethylpyrido[6,1-f]xanthine.See [1] for Communication 3.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1551–1554, November, 1987.     

Reaction of 2-chloroindole-3-carbaldehyde with epihalogenohydrins. Tandem oxirane-opening—1,3-oxazole-closure process

Reaction of 2-chloroindole-3-carbaldehyde with epibromohydrin gives the expected 1-(oxiran-2-ylmethyl) derivative. However the analogous reaction with epichlorohydrin leads to the formation of the oxazolo[3,2-a]indole skeleton. Some chemical properties of this tricyclic system were investigated. Its reaction with secondary amines unexpectedly proceeds with the opening of the oxazole ring.     

The dynamic structure of jadomycin B and the amino acid incorporation step of its biosynthesis

Jadomycin B, an antifungal antibiotic with a unique 8H-benz[b]oxazolo[3,2-f]phenanthridine pentacyclic skeleton produced by the bacterium Streptomyces venezuelae ISP 5230, exists in a dynamic equilibrium of two diastereomers differing in the configuration of C-3a. Several novel jadomycins with various amino acid-derived 1-side chains could be generated, by replacing isoleucine in the production medium of S. venezuelae with other amino acids. These two findings led to the conclusion that a nonenzymatic reaction with the amino acid followed by a likewise nonenzymatic cyclization cascade are crucial for its late biosynthesis.     

Synthesis,physicochemical properties,and mass spectrometric study of some 8-methyl-6H-thiazolo[3,2-f]xanthines

Alkylation of 8-mercapto-3-methylxanthine with -haloketones has given the corresponding aroylmethylthio-3-methylxanthines, from which have been obtained some novel 3-aryl-8-methyl-6H-thiazolo[3,2-f]xanthines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1534–1539, November, 1987.     

Aminomethylation of pemoline

Aminomethylation of pemoline with primary amines has given the corresponding oxazolo[3,2-a]-1,3,5-triazines or oxazolo[3,2-a]-1,3,5,7-tetrazocines. When secondary amines were used, the 5-amino- or 3,5-bis(aminomethyl) derivatives were obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1670–1674, December, 1990.The authors thank A. V. Dogadin for obtaining and discussing the PMR spectra.     

Heterocycles with a bridged nitrogen atom. 12. Recyclization of 5-methyloxazolo[3,2-a]pyridinium cation in the presence of acetylacetone. Crystal structure of 1-acetyl-2,5-dimethylindolizine

Reaction of 5-methyl-2-(p-nitrophenyl)oxazolo[3,2-a]pyridinium perchlorate with acetylacetone gives 1-acetyl-2,5-dimethylindolizine, the structure of which was proved by X-ray analysis.For communication 11 see [1].Dedicated to the anniversary of Professor M. A. Yurovskaya.M. V. Lomonosov State University, Moscow 119899, Russia; Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 401–405, March, 2000.     

Simple and Expedient Access to Novel Fluorinated Thiazolo- and Oxazolo[3,2-a]pyrimidin-7-one Derivatives and Their Functionalization via Palladium-Catalyzed Reactions

An efficient, versatile, and one-pot method for the preparation of novel fluorinated thiazolo- and oxazolo[3,2-a]pyrimidin-7-ones is described from 2-aminothiazoles or 2-amino-oxazoles and fluorinated alkynoates. This transformation, performed under transition-metal-free conditions, offers new fluorinated cyclized products with good to excellent yields. Moreover, the functionalization of these N-fused scaffolds via the Suzuki-Miyaura and Sonogashira cross-coupling reactions led to the synthesis of highly diverse thiazolo- and oxazolo[3,2-a]pyrimidin-7-ones.     

A novel heterocyclic compound. Synthesis and reactivities of an oxazolo[3,2-a]thieno[3,2-d]-pyrimidine derivative

A practical preparation of 2,3-dihydro-5H-oxazolo[3,2-a]thieno[3,2-d]pyrimidin-5-one (2) from methyl 3-aminothiophene-2-carboxylate in two steps was developed. The addition reactions of various nucleophiles to 2 were investigated and oxazole-ring-opened compounds were produced (5, 6, 12, 13 and 14). Desulfurization reaction of 2 with Raney Ni gave an oxazolo[3,2-a]pyrimidine derivative (15). It was found that 2 showed potent anti-gastric secretion activity.     

4-hydroxy-2-quinolones. 200*. Bromination of 1-<Emphasis Type="Italic">R</Emphasis>-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyridinylmethylene hydrazides

The behavior of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyridinylmethylene- hydrazides under bromination conditions using molecular bromine has been studied. It has been found that the 1-N-allyl derivative is characteristically halocyclized to the corresponding oxazolo[3,2-a]-quinoline, whereas the 1-N-hexyl-substituted acylhydrazone is unexpectedly brominated in the azomethine fragment.     

An easy route to 2‐substituted‐2,3‐dihydro‐5(7)H‐oxazolo[3,2‐a]pyrimidin‐5‐ones and 7‐ones starting from the corresponding 2‐amino‐2‐oxazolines

The isomeric 2‐substituted‐7(5)‐methyl‐2,3‐dihydro‐5(7)H‐oxazolo[3,2‐a]pyrimidin‐5‐ones 3a‐b and 7‐ones 2a‐b,7a were synthesized by cyclocondensation from the 5‐substituted‐2‐amino‐2‐oxazolines 1a‐b with biselectrophiles. In boiling ethanol, the reaction of 1a‐b with acetylenic esters led to a mixture of 2a‐b,7a with a small amount of (E)‐2‐N‐(2‐ethoxycarbonylethylene)‐5‐substituted‐2‐iminooxazolines 5a‐b . The ring annulation between 1a‐b and diketene gave the 2‐substituted‐7‐hydroxy‐7‐methyl‐2,3,6,7‐tetrahydro‐5H‐oxazolo[3,2‐ a ]pyrimidin‐5‐ones 4a‐b which can be easily dehydrated to provide the 2‐substituted‐7‐methyl‐2,3‐dihydro‐5H‐oxazolo[3,2‐a]pyrimidin‐5‐ones 3a‐b .     

[1,3]Oxazolo[3,2-b][1,2,4]triazoles: a versatile synthesis of a novel heterocycle

An efficient one-pot microwave approach for the synthesis of novel [1,3]oxazolo[3,2-b][1,2,4]triazoles is described.     

Thienooxazolopyrimidinium salts. Reaction of 1-bromomethyl-5-oxo-4-phenyl-1,2,4,5,6,7,8,9-octahydro[1]benzothieno-[3,2-<Emphasis Type="Italic">e</Emphasis>][1,3]oxazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidin-11-ium bromide with oxygen-centered nucleophiles

Reactions of [1]benzothieno[3,2-e][1,3]oxazolo[3,2-a]pyrimidin-11-ium bromide with oxygen-containing nucleophiles involve opening of the dihydrooxazole ring and lead to the formation of new functionally substituted thieno[2,3]-d]pyrimidine derivatives.     

Synthesis and rearrangement of cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones: an access to cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones

2-Substituted-4a-hydroxy-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 2a-c were synthesized by an one-step cyclocondensation from the 5-substituted-2-amino-2-oxazolines 1a-c with ethyl 2-oxocyclohexanecarboxylate in ethanol at room temperature, and easily dehydrated to provide 2-substituted-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 3. In refluxing xylene, the reaction conducted with various ethyl 2-oxocycloalkanecarboxylates led to the two isomeric 2-substituted-8/9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones 3 and 2-substituted-5H-cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones 4. The structure of some compounds was unambiguously established using X-ray crystallography. According to results from the DSC analysis of compound 2a, formation of the thermodynamically stable pyrimidinones 4 could be related to an intramolecular rearrangement of kinetically controlled pyrimidinones 3.     

Synthèse des pyrido[2,3-d] el [3,2-d] -s-triazolo[3,4-f] pyrimidines el de (pyrazolyl-1')-4 pyrido[2,3-d] et [3,2-d] pyrimidines

The synthesis of two new heterocycles is described: pyrido-[2,3-d]-.s-triazolo[ 3,4-f] pyrimidine and pyrido[3,2-d]-.s-triayzolo-[3,4-f] pyrimidine. 4-[I'-Pyrazolyl]pyrido[2,3-d]pyrimidines and 4-[1′-pyrazoly1] pyrido[ 3,2-d] pyrimidine are obtained by the action of 4-hydrazinopyrido[2,3-d]pyrimidine and 4-hydrazinopyrido-[3,2-d]pyrimidine with several β-diketones.     

Synthesis of new hetero[1,2,4]thiadiazin‐3‐one S,S‐dioxides and oxazolo[3,2‐b]hetero[1,2,4]thiadiazine S,S‐dioxides as potential psychotropic drugs

A series of 2‐substituted 2H‐thieno[3,4‐e][1,2,4]thiadiazin‐3(4H)‐one 1,1‐dioxides ( 2 ), 2‐substituted 2H‐thieno[2,3‐e][1,2,4]thiadiazin‐3(4H)‐one 1,1‐dioxides ( 3 ), 2‐substituted 4,6‐dihydropyrazolo[4,3‐e]‐[1,2,4]thiadiazin‐3(2H)‐one 1,1‐dioxides ( 4 ), 2‐substituted 2,3‐dihydrooxazolo[3,2‐b]thieno[3,4‐e]‐[1,2,4]thiadiazine 5,5‐dioxides, ( 5 ), 6‐substituted 6,7‐dihydro‐2H‐oxazolo[3,2‐b]pyrazolo[4,3‐e][1,2,4]thia‐diazine 9,9‐dioxides ( 6 ) and 7‐substituted 6,7‐dihydro‐2H‐oxazolo[3,2‐b]pyrazolo[4,3‐e][1,2,4]thiadiazine 9,9‐dioxides ( 7 ) were synthesized as potential psychotropic agents.     

Synthesis,anticancer and antimicrobiological activities of pyrrolo[2,3-d]pyrimidines

Reactions of 6-amino-3,4-dihydro-2-methoxy-4-oxopyrimidine 1a and its 3-methyl derivative 1b with chloroacetaldehyde and chloroacetyl chloride are discussed in this paper. Amongst others compounds, we have obtained, in low yield, the novel ring system oxazolo[3,2-c]pyrrolo[3,2-e]pyrimidine. The anticancer and antimicrobial activities of some of the obtained products are described.