Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-pyrazolo[3,4-d]pyrimidin-4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-4(5H)-ones with sulfuric acid.     

New heterocyclic structures. [1,2,5]Thiadiazolo[3′,4′:4,5]pyrimido-[2,1-b][1,3]thiazine and thiazolo[3,2a][1,2,5]thiadiazolo[3,4-d]pyrimidine

Derivatives of two new molecular structures, namely, 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one and 6,7-dihydro-9H-thiazolo[3,2-a][1,2,5]thiadiazolo[3,4-d][pyrimidin-9-one, and derivatives of N-substituted sulfamic acid, namely, (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-on-7-yl)sulfamic acid and (7-amino-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin-5-on-6-yl)sulfamic acid, were separated out as by-products in the reduction reaction of 8-amino-3,4-dihydro-7-nitroso-2H,6H-pyrimido[2,1- b][1,3]thiazin-6-one and 7-amino-2,3-dihydro-6-nitroso-5H-thiazolo[3,2-a]pyrimidin-5-one derivatives, respectively, with sodium hydrosulfite. A mechanism of reaction, which hypothesizes the action of sodium hydrosulfite in an asymmetic form, is proposed. The results of single-crystal X-ray investigation on 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one (R = 0.032 for 863 reflections) and (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b]- [1,3]thiazin-6-on-7-yl)sulfamic acid, sodium salt (R = 0.028 for 3507 reflections) are reported.     

Synthesis of diarylazolo[<Emphasis Type="Italic">a</Emphasis>]pyridines from [(<Emphasis Type="Italic">Z</Emphasis>)-2,4-diaryl-4-oxo-2-butenyl]azolium salts

A method for the synthesis of derivatives of [1, 3]thiazolo[3,2-a]pyridines, pyrido[2,1-b][1, 3]benzo-thiazole, [1, 3, 4]thiadiazolo[3,2-a]pyridine, and [1, 2, 4]triazolo[4,3-a]pyridine, which includes base initiated cyclization of quaternary azolium salts, formed by the interaction of (Z)-1,3-diaryl-4-bromo-2-buten-1-ones with 1-alkyl-1H-1,2,4-triazoles, 4-methyl-1,3-thiazole, 1,3-benzothiazole, and N-phenyl-1,3,4-thiadiazole-2-amine. Derivatives of 2-chloroimidazo[1,2-a]pyridine were obtained when 5-chloro-1-methyl-1H-imidazole was used.     

Cyclization reactions of 1,3-dibromopropan-2-ol, 2,3-dibromopropan-1-ol and 1-bromomethyloxirane with 6-amino-2,3-dihydro-2-thioxo-4(1H)-pyrimidinone

The cyclization reactions, carried out in strongly- or weakly-basic media, are described. Sometimes, 7-amino-2,3-dihydro-3-hydroxymethyl-5H-thiazolo[3,2-a]pyrimidin-5-one is separated out, together with 8-amino-3,4-dihydro-3-hydroxy-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one, as the principal product. A mechanism of reaction, during which the cyclizating agents are changed into oxirane derivatives, is proposed. The results of single-crystal X-ray investigations on 8-amino-3,4-dihydro-3-hydroxy-7-nitroso-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one (R = 0.035 for 1013 reflections), and on 7-hydroxymethyl-6,7-dihydrothiazolo[3,2-a][1,2,3]triazolo[4,5-d]pyrimidin-9(1H)-one (R = 0.027 for 1607 reflections) are reported.     

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 of novel spiro[benzo[4,5]thiazolo[3,2-a]chromeno[2,3-d]pyrimidine-14,3′-indoline]-1,2′,13(2H)-triones via three component reaction

A new and efficient method for the synthesis of hitherto unreported spiro[benzo[4,5]thiazolo[3,2-a]chromeno[2,3-d]pyrimidine-14,3′-indoline]-1,2′,13(2H)-triones was developed via the Domino Knoevenagel condensation–Michael addition–intermolecular cyclization sequences of isatin derivatives, cyclohexane-1,3-diones, and 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-ones, employing 12-tungstophosphoric acid (H₃PW₁₂O₄₀) as an effective and inexpensive catalyst.     

Synthesis and antimicrobial activity of new derivatives of pyrano[4',3':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine and new heterocyclic systems

Taking into account previously obtained biological results on some polyheterocyclic compounds (containing different heteroatoms) and in particular on several 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines Ia-v we have carried out the synthesis of twentyone 8-amino-5-isobutyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines 6. Therefore we have slightly modified the structure of the previously studied I introducing at C-5 an isobutyl group instead of the previously examined isopropyl ones in order to see if this variation (changing a little the lipophilicity) will affect the biological activity. Furthermore thieno[3,2-d]pyrimidine-8-thione 7 and their S-alkylated 8 were synthesized. Finally by alkylation of 5-isobutyl-2,2-dimethyl-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-8(9H)-one 3 with alkyl dichlorides (bifunctional reagents) we realized the cyclization of a thiazole or thiazine ring on the [b] side of the pyrimidine ring with formation of the new condensed pentaheterocyclic systems: pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin-8-one 11 and pyrano[4''',3''':4'',5'']pyrido[3'',2'':4',5']thieno[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-8-one 12. It was found that some of the synthesized compounds showed interesting antimicrobial activity (by agar diffusion method) against some gram-positive and gram-negative bacilli strains.     

Synthesis of pyrido[2,3-d]pyrimidin-4-one derivatives

This paper describes one-pot synthesis of 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidin-5-one 4 , 5H-dipyri-do[1,2-a:3′,2′-e]pyrimidin-5-one 10 and 5H-pyrido[3,2-e]pyrimido[1,2-a]pyrimidin-5-one 15 and some of their derivatives, starting with 2-chloro-3-pyridine carboxilic acid 1. Compounds 4 and 10 reacted with phosphorus pentasulfide to give the respective 5-thione analogues, 5 from 4 and 11 from 10 . Boiling the 5-thione derivatives with hydrazine hydrate, the respective 5-hydrazono derivatives 6 from 5 and 12 from 11 were obtained. The 5-acetyl hydrazono, 7 , and the 5-isopropylidenehydrazono, 8 , derivatives were also prepared from 6 , and the 5-propionylhydrazono derivatives, 13 , from 12 . Compound 4 reacted with hydrazine to give an adduct with two molecules of hydrazine and the probable structure 16 . Treating this adduct with acetone a monohydrazone 17 was obtained. Boiling a suspension of this adduct in DMF, it gave 6,10-dihydro-6H-pyrido[3′,2′:5,6]pyrimido[2,1-c][1,2,4]triazin-5-one 20 .     

Synthesis,Reactions, and Antimicrobial Evaluation of Some Polycondensed Thienopyrimidine Derivatives

Some novel indeno[2,1-b]thiophenes, indeno[1′,2′:4,5]thieno[2,3-d][1,2,3]triazines, indeno[1′,2′:4,5]thieno[2,3-d]pyrimidines, indeno[1′,2′:4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidines, and indeno[1′,2′:4,5]thieno[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines 2–16 were prepared starting with 2-aminoindeno[2,1-b]thiophene-3-carboxylic acid amide ( 1 ). Furthermore, the antimicrobial evaluation of the prepared products showed that many of them revealed promising antimicrobial activity.     

Reactions of 2-(2-propynylsulfanyl)-5,6,7,8-tetrahydrobenzo[<Emphasis Type="Italic">b</Emphasis>]thieno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(<Emphasis Type="Italic">3H</Emphasis>)-one with arylsulfenyl chlorides

2-(2-propynylsulfanyl)-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-4(3H)-one with arylsulfenyl chlorides in chloroform gave products of anti-Markownikoff Ad _E-addition. The use of nitromethane as solvent in the presence of lithium perchlorate additives favored intramolecular electrophilic cyclization into 1-arylsulfanyl-1,2,6,7,8,9-hexahydro-4H-benzo[4,5]thieno[3,2-e][1,3]thiazolo[3,2-a]-pyrimidin-5-one.     

Iodocyclization of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

Iodination of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3H)-ones was accompanied by cyclization to 2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodides. 3-(Iodomethyl)-3-methyl- 7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodide was reduced with sodium iodide to 3,3-dimethyl-7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium iodide.     

Synthesis of 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives

The reaction of 2-aminothiazoles with ethyl acetoacetate in acetic or polyphosphoric acid gave a series of 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives which were nitrated with a mixture of nitric and sulfuric acid to 6-nitro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-ones, and the latter were reduced to the corresponding amines.     

Fused pyrimidine systems: XVI. Electrophilic intramolecular cyclization of 2-(alkenylsulfanyl)pteridin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

2-[Allyl(but-3-en-1-yl, pent-4-en-1-yl)sulfanyl]pteridin-4(3Н)-ones at heating in polyphosphoric acid undergo an intramolecular cyclization affording respectively 9-methyl-8,9-dihydro-5H-[1,3]thiazolo[3,2-a] pteridin-5-one and 10-methyl(ethyl)-9,10-dihydro-5Н,8Н-[1,3]thiazino[3,2-a]pteridin-5-ones of angular structure. The cyclization of 2-(alkenylsulfanyl)pteridin-4(3Н)-ones under the action of iodine or arylsulfenyl chlorides afforded iodo(arylsulfanyl) derivatives of angularly fuzed thiazolo- and thiazinopteridines.     

Action of 1,2-diamines and o-aminophenols on 1-alkyl-3-carboxyindole-2-acetic acid anhydrides. Preparation of new ring systems

1-Alkyl-3-carboxyindole-2-acetic acid anhydrides (I) react with ethylenediamine and with o-phenylenediamine to give directly 10-alkylimidazo[3,2:1′,2′]pyrido[4,5-b]indol-5(1H)-ones (II) and 5,6-dihydro-5-alkyl-13H-indolo[2′,3′:4,5]pyrido[1,2-a]benzimidazol-13-one (V), respectively. However, anhydrides I react with o-aminophenol and with o-aminothiophenol to give carboxyindole-acetanilide derivatives IX, which can be cyclised to indolo[2′,3′:4,5]pyrido[2,1-b]benzoxazolone and indolo[2′,3′:4,5]pyrido[2,1-b]benzthiazolone (XI). Some derivatives of II and V were prepared to help in elucidating the structures.     

A new strategy for the synthesis of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines

A series of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines were prepared via oxidative cyclization of aldehyde N-(1,3-diphenylpyrazolo[3,4-d]pyrimidin-4-yl)hydrazones. Dimroth rearrangement of such a series yielded pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines.     

New [g]-fused [1,2,4]triazolo[1,5-c]pyrimidines: Synthesis of pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-c]pteridine derivatives

A number of 2-aryl-substituted pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-c]pteridines 11,12a,b,e , their corresponding 5-carbonyl derivatives 7,8a,b,e and some pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5-ones 7,8c,d have been synthesized, according to different pathways. The new tricyclic heterocycles were prepared with the aim of studying their possible benzodiazepine receptors affinity.     

Intramolecular N-arylation in heterocyclization: synthesis of new pyrido-fused pyrrolo[1,2-a][1,4]diazepinones

Alkylation of l-prolinamide with 3-(chloromethyl)-2-halopyridines, followed by cyclization through an intramolecular Pd-catalysed amidation, provided an entry to the pyrido[2,3-e]pyrrolo[1,2-a][1,4]diazepin-10-one scaffold. Furthermore, a synthetic route towards diverse new pyrido[f]pyrrolo[1,2-a][1,4]diazepin-7-ones has been developed by acylation of contiguously substituted (aminomethyl)halopyridines with Boc-l-proline followed by intramolecular amination.     

Synthesis of new condensed derivatives of pyrano[4,3-<Emphasis Type="Italic">b</Emphasis>]thieno[3,2-<Emphasis Type="Italic">e</Emphasis>]pyridine and pyrido[3',2':4,5]thieno[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidine

The reactions of 2-methyl (propyl) substituted 8,8-dimethyl-7,10-dihydro-4H,8H-pyrano[3",4":5',6']pyrido[3',2':4,5]thieno[3,2-d][1,3]oxazines with primary amines give 2-methyl (propyl) substituted 8,8-di- methyl-7,10-dihydro-8H-pyrano[3",4":5',6']pyrido[3',2':4,5]thieno[3,2-d][1,3]pyrimidin-4(3H)-ones or 3-acetyl-N-alkyl- and N-alkyl-3-butyrylamino-7,7-dimethyl-7,8-dihydro-5H-pyrano[4,3-b]thieno[3,2-e]- pyridine-2-carboxamides depending on steric hindrance in the amines.     

Synthesis of [1,3,4]thiadiazolo[3,2-a]pyrimidines in the presence of formic acid

Formic acid-phosphorus pentoxide was effective for the preparation of 5,7-dimethyl[1,3,4]thiadiazolo- and -[1,3]thiazolo[3,2-a]pyrimidin-4-ium salts. Further, the pyrimidine ring transformation and the isocyanation of 5imino-6H-[1,3,4]thiadiazolo- and -[1,3]thiazolo[3,2-a]pyrimidin-7-ones were carried out in the presence of formic acid and triethyl orthoformate, respectively.     

Synthesis of 7-oxindolylidene-3a,9a-diphenylimidazothiazolo[2,3-c][1,2,4]triazines by skeletal rearrangement of their [3,2-b]-fused isomers

Previously unavailable 7-oxindolylidene-1,3-dimethyl-3a,9adiphenylimidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines were obtained in 63–90% yields by skeletal amidine rearrangement of the thiazolo-triazine system in the corresponding imidazo[4,5-e]thiazolo[3,2-b][1,2,4]triazines on treatment with sodium methoxide.