Transformations of 5-methyl-6-carbethoxy-3,4-dihydrothieno-[2,3-d]pyrimidine for synthesis of 4-methoxy-, 4-alkylamino-, and other derivatives of thieno[2,3-d]pyrimidine

4-Chloro derivatives of thieno[2,3-d]pyrimidine are formed by the action of phosphorus oxychloride on 5-methyl- and 5-methyl-6-carbethoxythieno[2,3-d]pyrimidin-4-ones. Action of nucleophilic reagents (methanol, sodium methylate, primary and secondary amines) on these chloro derivatives gave 4-methoxy-, 4-alkylamino-, and 4-dialkylamino substituted thieno[2,3-d]pyrimidines. It was found that 4-methoxy derivatives of thieno[2,3-d]pyrimidines undergo a thermal rearrangement into 3-methyl-substituted thieno[2,3-d]pyrimid-4-ones. In the bromination of 5-methyl-4-chloro- and 5-methyl-4-methoxy-substituted thieno[2,3-d]pyrimidines by N-bromosuccinimide, 5-bromomethyl derivatives of thieno[2,3-d]pyrimidine are formed, from which, by the action of primary and secondary amines, 5-aminomethyl-substituted thieno[2,3-d]pyrimidines were obtained. A synthesis of 1,2,3,4-tetrahydro-1,3-diazepino[4a,10-d,e] thieno[2,3-d]pyrimidines was also carried out.Deceased.Translated from Khimiya Geterotsilicheskikh Soedinenii, No. 7, pp. 925–928, July, 1985.     

Multistep, microwave assisted, solvent free synthesis and antibacterial activity of 6-substituted-2,3,4-trihydropyrimido[1,2-c]9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines

A novel, efficient, microwave assisted route for the synthesis of 6-substituted-2,3,4-trihydropyrimido[1,2-c]-9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines in good yields has been developed. The intermediates, 2-substituted-4-[3-hydroxy(propyl-1-amino)]5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines were obtained by irradiating 2-substituted-4-chloro-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines with 1-amino-propanol under basic conditions in a microwave oven. 4-Chlorothieno[2,3-d]pyrimidines were synthesized by microwave irradiation of equimolar mixture of 4-hydroxythieno[2,3-d]pyrimidines and phosphorus oxychloride. The final compounds were screened for antibacterial activity by Kirby Bauer's method using amicacin as the standard against various gram positive and gram negative bacteria. All the compounds showed antibacterial activity comparable with the standard.     

Synthesis and antibacterial activity of some novel triazolothienopyrimidines

A novel series of some novel 5-substituted-1,2,4-triazolo[4,3-c]8,9,10-trihydrocyclopenta/8,9,10,11,12-pentahydrocyclohepta[b]thieno[3,2-e]pyrimidin-3-thiones has been synthesized. The intermediates 4-chloro-2-substituted-5,6,7-trihydrocyclopenta/5,6,7,8,9-pentahydrocyclohepta[b]thieno[2,3-d]pyrimidines were prepared by warming 2-substituted-5,6,7-trihydrocyclopenta/5,6,7,8,9-pentahydrocyclohepta[b]thieno[2,3-d]pyrimidin-4[3H]-ones with oxalyl chloride. Thieno[2,3-d]pyrimidin-4[3H]-ones were prepared by a novel, microwave assisted, solvent free, synthetic route under basic conditions hitherto unreported in the literature from ortho amino ester of thiophene. The chloro derivatives, without further purification, were hydrazinated to yield 2-substituted-4-hydrazino-5,6,7-trihydrocyclopenta/5,6,7,8,9-pentahydrocyclohepta[b]thieno[2,3-d]pyrimidines. These compounds were cyclized with carbon disulphide to give the title compounds in quantitative yields. The final compounds were screened for antibacterial activity by Kirby Bauer's method using ampicillin as the standard against various gram positive and gram negative bacteria. All the compounds showed antibacterial activity comparable with the standard.     

Synthesis of Novel Pyrrylthieno[2,3-d]Pyrimidines and Related Pyrrolo[1″,2″:1″,6″]Pyrazino[2″,3″:4,5]Thieno[2,3-d]Pyrimidines

4-Methyl-2-phenyl-5-(1-pyrryl)-6-substituted-thieno[2,3-d]pyrimidines ( 3a-c , 4a-c , 5a , b , and 6 ) have been synthesized. Some of the substituents in position 6 were used to build up different sulfur-, nitrogen- and/or oxygen-containing heterocyclic rings at that position. The 4-methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]pyrimidine-6-carboazide ( 20 ) was also used as a key intermediate in the synthesis of the target pyrrolo[1",2":1',6']pyrazino[2',3':4,5]thieno[2,3-d]pyrimidines.     

Zn(OAc)2 catalyzed microwave irradiated synthesis of substituted thieno[2,3-d]pyrimidin-4(3H)-one

Different Lewis acids were screened to catalyze the reaction of 2-amino-thiophene-3-carboxylate, orthoformate and aryl amine to form 2-substituted thieno[2,3-d]pyrimidin-4(3H)-one. Zn(OAc)₂ was demonstrated to efficiently catalyze the reaction. 20 substituted thieno[2,3-d]pyrimidines were synthesized by adding 0.5% mol Zn(OAc)₂ as catalyst under microwave irradiation.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Synthesis of 2,3-disubstituted derivatives of pyrano-, thiopyrano-, and benzoannelated pyrido[2,3-<Emphasis Type="Italic">b</Emphasis>]thieno[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

A new methods have been developed for the synthesis of condensed pyrido[2,3-b]thieno[3,2-d]pyrimidines based on cyclic derivatives of 4-cyanopyridine-3-thiones. The presence of two different reactive functional groups NH₂ and CONH gives the possibility of carrying out different conversions of thieno[2,3-b]pyridines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1245–1252, August, 2008.     

Regioselective synthesis of 5,6-polymethylene-3-cyanopyridine-2(1H)-thiones and fused heterocycles based on them

Condensation of 2-hydroxymethylenecyclopentan-1-one or -cyclooctan-1-one sodium salts with cyanothioacetamide afforded 5,6-polymethylene-3-cyanopyridine-2(1H)-thiones which were regioselectively alkylated at the sulfur atom by alkyl halides. Derivatives of 3-cyanopyridine-2(1H)-thione and 2-alkylthio-3-cyanopyridine were used for regioselective synthesis of substituted heterocycles: 3-aminothieno[2,3-b]pyridines, pyrido[2,3∶2′,3′]thieno[4,5-d]pyrimidines, and pyrido[2,3∶2′,3′]thieno[4,5-d]oxazines.     

A Convenient Synthesis for Some New Pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines and Related Fused 1,2,4-Triazolo and 1,3,4-Thiadiazolo-derivatives

Diethyl 2-isothiocyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6 dicarboxylate 1 is a convenient and useful starting matrial for the constructions of heterocyclic systems. It was utilized to synthesize derivatives of the novel heterocyclic systems pyrido[4',3':4,5]thieno[2,3-d]pyrimidine 4 , 10 , pyrido[4',3':4,5]thieno[2,3-d]-[1,2,4]triazolo[1,5-a]pyrimidine 7 , 11a-e and pyrido[4',3':4,5]thieno[2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidine 12-14 .     

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.     

Condensed thienopyrimidines. II. Synthesis and gastric antisecretory activity of thiazole and polymethylene condensed thienopyrimidine derivatives

Thiazolo[3,2-a]thieno[3,2-d]-, [3,4-d]- and [2,3-d]pyrimidin-5-one derivatives (6, 11 and 16), and polymethylene condensed thieno[3,2-d]-, [3,4-d]- and [2,3-d]pyrimidin-5-one derivatives (19-21), in which the oxygen atom of the oxazolidine moiety in 3 was replaced by a sulfur atom or methylene groups, were synthesized and evaluated for gastric antisecretory activity in pylorus-ligated rats. The structure-activity relationships of these compounds are discussed.     

Thiazolo(oxazolo)thieno[b]pyrimidines. Preparation from 2-allylthio(oxy)thieno[2,3-d]pyrimidines and hydrolysis

Heterocyclization of 5,6-disubstituted 2-allylthio(oxy)-4-oxothieno[2,3-d]pyrimidines by treatment with halogens affords thieno[3,2-e]thiazolo[3,2-a]pyrimidine iminium salts. Treatment of these salts with aqueous sodium acetate results in cleavage of the thiazoline ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 413–418, March, 1989.     

RECENT TRENDS IN THE CHEMISTRY OF THIENOPYRIDAZINES

This review describes the synthesis of thieno[2,3-c]pyridazine, thieno [3,2-c]pyridazine, thieno[2,3-d]pyridazine and thieno[3,4-d]pyridazine derivatives and their reactions.     

Reversible carboxamide-mediated internal activation at C(6) of 2-chloro-4-anilino-1H-pyrrolo[2,3-d]pyrimidines

A synthetic route to bisanilino-1H-pyrrolo[2,3-d]pyrimidines has been discovered, wherein the C(6)-chloride reactivity is necessarily enhanced via reversible acid-catalyzed internal activation of the pyrimidine ring by a C(1')-carboxamide moiety. Subsequent selective nucleophilic displacements at C(6) and C(1') constitute a one-pot tandem protocol for the rapid assembly of bisanilino-1H-pyrrolo[2,3-d]pyrimidines.     

Derivatives of Condensed Thienopyrimidimines. 13. Synthesis and Structure of Pyrano[4',3':4,5]thieno[3,2-e]-1,2,4-triazolo[2,3-c]pyrimidines

Methods for the synthesis of 5-substituted 10,10-dimethyl-10,11-dihydro-8H-pyrano[4',3':4,5]thieno[3,2-e]-1,2,4-triazolo[2,3-c]pyrimidines have been developed. An X-ray crystallographic study of 5-(2-ethoxymethylhydrazino)-10,10-dimethyl-10,11-dihydro-8H-pyrano[4',3':4,5]thieno[3,2-e]-1,2,4-triazolo[2,3-c]pyrimidine has been carried out.     

Functional derivatives of thiophene

A method is proposed for the synthesis of 5-acylamino-2,3-dimethylthiophene-4-carbaldehydes and 5-acylamino-2,3-tetramethylenethiophene-4-carbaldehydes by the formylation of the corresponding thiophenes using the Vilsmeier reaction. From the formyl derivatives obtained, previously unaccessible derivatives of thieno[2,3-b]pyridine, thieno[2,3-d]pyrimidine, and thieno[3′,2′∶5,6]pyrido[2,3-d]-pyrimidine have been synthesized.     

Transformations of tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-ones in the presence of alkynes bearing electron-withdrawing substituents

Tetrahydropyrido[4??,3??:4,5]thieno[2,3-d]pyrimidines in the presence of activated alkynes were transformed into mixtures of pyrimido[5??,4??:4,5]thieno[3,2-d]azocines and spiro[pyridine-4,5??-thieno[2,3-d]pyrimidines].     

Synthesis and properties of 1-aryl-2,5,7-trimethyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines

1-Aryl-2,5,7-trimethyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines are formed from the cyclization of N-acetyl-2-arylamino-4,6-dimethylnicotinonitriles by perchloric acid in a mixture of acetic acid and acetic anhydride. 1-Aryl-2-acetonyl-5,7-dimethyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines areformedonheating2-arylamino-4,6-dimethylnicotinamides with acetic anhydride. These and analogous compounds were obtained by acylation of 1-aryl-2,5,7-trimethyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines with acetic anhydride or benzoyl chloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1234–1236, September, 1992.     

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.     

顺序一锅法合成5,6,8-三氢-吡喃并[3’,4’:4,5]噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物

采用顺序一锅法,以4,5,7-三氢-吡喃并[4,3-d]噻吩基三苯基膦亚胺、芳基异氰酸酯和胺类化合物为原料,合成了19个结构新颖的5,6,8-三氢-吡喃并[3’,4’:4,5]噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物.该方法具有条件温和、操作简便、收率高等特点.所得化合物的结构用1H NMR,IR和MS等手段进行了表征,此外还通过X射线单晶衍射分析法进一步确证了化合物3-(4-氯苯基)-2-二乙胺基-5,6,8-三氢-吡喃并[3’,4’:4,5]噻吩并[2,3-d]嘧啶-4(3H)-酮(4a)的结构.