Synthesis and antileukemic activity of spiro[indoline-3,2′-thiazolidine]-2,4′-diones

A number of spiro[indoline-3,2′-thiazolidine]-2,4′-diones have been prepared via the cyclocondensation of isatin-3-imines with α-mercaptoacids. 1-Benzyl-5′,5′-dimethylspiro[indoline-3,2′-thiazolidine]-2,4′-diones were prepared by simultaneously refluxing 1-benzylisatin, α-mercaptoisobutyric acid and various anilines in toluene. 3′-(4-Chlorophenyl)-5,5′-dimethylspiro[indoline-3,2′-thiazolidine]-2,4′-dione was active in the P388 and the L1210 leukemia screen tests. A number of analogs of the active spiro compound have been prepared and submitted for antileukemic screening. Anticonvulsant screening results of related compounds are also included.     

Synthesis of spiro[3H-indole-3,2′-tetrahydro-1,3-thiazine]-2,4′(1H)-diones

The title compounds have been prepared by the cyclocondensation of 3-mercaptopropanoic acid with isat-in-3-imines. The 1-benzyl derivatives have been synthesized by simultaneously reacting 1-benzylisatin, substituted anilines and 3-mercaptopropanoic acid. Mannich condensation of the spiro thiazanones with secondary amines gave the corresponding 1-aminomethyl derivatives.     

Synthesis of 2,4′-dioxospiro[indoline-3,2′-thiazolidine]-5′-acetic acids: X-ray structure of 1-benzyl-3′-(4-chlorophenyl)-2,4′-dioxospiro- [indoline-3,2′-thiazolidine]-5′-acetic acid

The title compounds have been prepared by the cyclocondensation of mercaptosuccinic acid with isatin-3-imines. The 1-benzyl derivatives have been synthesized by simultaneously reacting 1-benzylisatin, substituted anilines and mercaptosuccinic acid. The structure of the products has been confirmed by X-ray diffraction measurements.     

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 pyrido[3′,2′:4,5] thieno[3,2-d]pyrimidine derivatives

Pyrido [3′,2′:4,5]thieno[3,2-d] pyrimidine and several of its derivatives have been synthesized.     

Nitration of dithieno[3,2-b:3′,2′-d]pyridine and dithieno[3,2-b:3′,4′-d]pyridine

Nitration of dithieno[3,2-b:3′,2′-d]pyridine ( 4 ) and dithieno[3,2-b:3′,4′-d]pyridine ( 5 ) has been studied. Nitration of 4 occurred in both positions of the C ring, while 5 was predominantly substituted on the 3,4-fused ring. The structures of the nitro derivatives were proven by extensive use of ¹H and ¹³C nmr spectroscopy.     

Synthesis of 5H-Triazolo[1,5-d]- and 5H- Tetrazolo- [1,5-d]thieno[3,2-f]-1,4-diazepin-6(7H)-ones

5H-Triazolo[1,5-d]- and 5H-tetrazolo[1,5-d]thieno[3,2-f]-1,4-diazepin-6(7H)-ones have been obtained by the base catalysed ring expansion reaction of 5-chloromethyl-1,2,4-triazolo[1,5-c]- and 5-chloromethyltetrazolo- [1,5-c]thieno[3,2-e]pyrimidines. The required thienopyrimidine derivatives were synthesized from 2-amino-3-triazolyl- and 2-amino-3-tetrazolylthiophenes by acylation, followed by dehydrative cyclization.     

The synthesis and transformations of 2-ethoxycarbonyl-3-isothiocyanatopyridine. Pyrido[3,2-d]pyrimidines and some azolopyrido[3,2-d]pyrimidines

2-Ethoxycarbonyl-3-isothiocyanatopyridine ( 2 ), prepared from 3-amino-2-ethoxycarbonylpyridine ( 1 ) by the thiophosgene method, was converted with nucleophiles into pyrido[3,2-d]pyrimidine derivatives 6–11 and 25–30 either directly, or through thiourethane 3 . Tricyclic systems 18 and 19 were obtained from 3 , and tricyclic systems 12–17 from pyrido[3,2-d]pyrimidine derivative 11 . Pyrrole reacted with 2 at C₂ to give 20 , and by further cyclization 21 and 22 .     

1,2-fused pyrimidines. V. Synthesis of 1-alkyl or phenyl-2H-dipyrido-[1,2-a:2′,3′-d]pyrimidine-2,5(1H)-diones

The reaction of 2-[(N-acyl, N-alkyl or phenyl)amino]-4H-pyrido[1,2-a]pyrimidin-4-ones 8a-g with the N,N-dimethylformamide/phosphorus oxychloride Vilsmeier reagent 1 (95°, 90 minutes) afforded 1-alkyl or phenyl-2H-dipyrido[1,2-a:2′,3′-d]pyrimidine-2,5(1H)^?diones, 3-alkyl substituted or not, 10a-g . The starting compounds 8 were prepared by treating 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones N-alkyl substituted 7a,b or N-phenyl substituted 4 with excess anhydrides (130°, 7 hours) when the 2-(alkylamino) derivatives 7 were used in the reaction, compounds 8 were obtained along with very small amounts of 3-acyl-2-(alkylamino)-4H-pyrido[1,2-a]pyrimidin-4-ones 9 .     

One-pot Synthesis of 2,4-Diamino-substituted Thieno[3,2-d]pyrimidines

An efficient one‐pot synthetic approach to 2,4‐diamino‐substituted thieno[3,2‐d]pyrimidines from 2,4‐dichlorothieno[3,2‐d]pyrimidine was described.     

“One pot” synthesis of 2-substituted 9-(2′-hydroxy-3′-aminopropyl)-8-azahypoxanthines and 8-azaadenines (5-substituted 3-(2′-hydroxy-3′-aminopropyl) 7-amino and 7-hydroxy-3H-1,2,3-triazolo[4,5-d]pyrimidines)

An example of the generalization of the synthesis of 8-azahypoxanthines A and 8-azaadenines B , interesting from a medicinal point of view, is presented by utilizing l-amino-2-hydroxy-3-azidopropanes.     

A polarographic study of the iron-2-hydroxymethyl-6-(2′-hydroxymethyl-5′-hydroxy-4′-pyrone-6′)-pyranyl-3,2[b]pyran-4,8-dione complex

A polarographic study has been carried out on the colored product formed in the interaction of iron(III) with 2-hydroxymethyl-6-(2′-hydroxymethyl-5′-hydroxy-4′-pyrone-6′)-pyranyl-3,2[b]pyran-4,8-dione. Measurements using the differential pulse method show that iron(III) exhibits a coordination number of 2 and a reproducible formation constant that varies somewhat depending upon the supporting electrolyte employed.     

Synthesis of spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones,spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones and spiro[benzofuran-2,1′-isobenzofuran]-3,3′-diones via transannular reactions of eight membered ring intermediates

An auto oxidation-rearrangement product 4 was isolated from a high dilution reaction of ninhydrin with 3,4,5-trimethoxyaniline in water. A general synthesis of this compound and its derivatives 4–6 was devised by oxidation of tetrahydroindeno[1,2-b]indol-10-ones 1–3 with sodium periodate to give isoindolo[2,1-a]-indole-6,11-diones 4–6 in good yield. Compounds 4–6 can be easily transformed into spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones 8–10 , spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones 11–13 and isoindole[1,2-a:2′,1′-b]pyrimidine-5,15-diones 15, 16 in high yields. Analogous reactions were performed on 3-amino-5a, 10a-dihydroxybenzo[b]indeno[2,1-d]furan-10-one ( 17 ) to give a dibenzoxocintrione 18 , spiro-[benzofuran-2,1′-isobenzofuran]-3,3′-dione 19 and an isoindol-1-one 20 .     

Synthesis of 5′-halo-2′,3′-lyxo-epoxy and 2′,3′-unsaturated thieno[3,2-d]pyrimidine nucleosides

A series of thieno[3,2-d]pyrimidine-2,4-dione nucleosides modified in the carbohydrate moiety has been synthesized. In the first part, synthetic routes are described for the replacement of 5′-hydroxyl group in preformed 1-(β-D-ribofuranosyl)thieno[3,2-d]pyrimidine-2,4-dione I by fluoro, iodo or chloro atoms. Reduction of the 5′-iodo substituent of VI was then carried out catalytically using palladium on carbon as catalyst to give the expected 5′-deoxy derivative VIII. The lyxo-epoxide derivative XII was then synthesized by sequential treatment of the 5′-deoxy-5′-chloro derivative X with methanesulfonyl chloride and with sodium hydroxide. In the second part, most of attention has been devoted to apply different methods reported in the literature that allow access to 2′,3′-olefinic derivatives from the corresponding 2′,3′-dihydroxy precursor. The 5′-O-silyl protected bisxanthate XIV either on reduction with tri-n-butyltin hydride or by reductive elimination of the haloacetate XVI afforded the free 2′,3′-olefin nucleoside after removal of the 5′-protecting group. However none of the compounds in this series exhibited significant antiviral activity against HIV at the doses tested.     

Studies on the synthesis of 2-(2-arylvinyl)thieno[2,3-d]pyrimidines and 5-(2-arylvinyl)triazolothieno[3,2-e]pyrimidines

Synthesis of 2-(2-arylvinyl)thienopyrimidines, by the acid catalyzed condensation of nitriles with thiophene o-aminocarbonyl compounds, the condensation of aldehydes with thiophene o-aminoamides, the base catalyzed condensation of aldehydes with 2-methylthienopyrimidines and by the Wittig condensation of 2-thieno-pyrimidinylmethylphosphonium salts with aldehydes is described. Isomeric 5-methyltriazolothienopyrimidines were found to react, under basic condition, with aldehydes yielding 5-(2-arylvinyl)triazolo[2,3-c]thieno-pyrimidines. While 5-styryltriazolo[4,3-c] isomers resisted acid catalysed isomerization, they were found to isomerize to triazolo[2,3-c]pyrimidines under base catalysis.     

Synthesis of New Fused Thieno[3,2-d]pyrimidines Based on Thieno[3,2-d][1,3]oxazine Derivative

Russian Journal of General Chemistry - A method was developed for the synthesis of new fused amines, thieno[3,2-d]pyrimidine derivatives, starting from the corresponding chloride and various...     

Pyrrolopyrimidines. 3. 5-Amino-1,3-dimethylpyrrolo-[3,2-d]pyrimidine-2,4-dione

Reaction of 5-amino-1,3-dimethylpyrrolo[3,2-d]pyrimidine-2,4-(1H,3H)-diones with -diketones produces enaminoketones. Some of these are converted by Lewis acids into pyrrolopyridazines.For No. 2, see [1].Rostov-on-Don State University, Rostov-on-Don 344090, Russia; e-mail: zeb@chimfak.rud.runnet.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 375–380, March, 1999.