Syntheses of some new azolopyrido‐[4′,3′:4,5]thieno[2,3‐d]pyrimidines

Diethyl 2‐[(ethoxythioxomethyl)amino]‐4,5,6,7‐tetrahydrothieno[2,3‐c]‐pyridine‐3,6‐dicarboxylate 2 , prepared from diethyl 2‐isothiocyanato‐4,5,6,7‐tetrahydrothieno[2,3‐c]pyridine‐3,6‐dicarboxylate 1 by boiling in anhydrous ethanol, was converted into pyrido[4′,3′:4,5]thieno[2,3‐d]pyrimidine derivatives 3, 4 by treatment with hydrazine hydrate. The tetracyclic systems imidazo[1,2‐a]pyrido‐[4′,3′:4,5]thieno[2,3‐d]pyrimidine 9 and pyrido[4′,3′:4,5]thieno[2,3‐d][1,3]thiazolo‐[3,2‐a]pyrimidine 10 were synthesized by the reaction of 2 with 1,2‐diaminoethane and aminoethanethiol, respectively. The hydrazino derivative 4 underwent cyclization reactions with orthoesters and nitrous acid to give the corresponding pyrido[4′,3′:4,5]thieno[2,3‐d][1,2,4]triazolo[1,5‐a]pyrimidines 5, 6 and pyrido[4′,3′:4,5]thieno[3,2‐e][1,2,3,4]tetrazolo[1,5‐a]pyrimidine 8 , respectively. Moreover, reactions of 3 with cyanogen bromide, N‐carbethoxyhydrazine, carbon disulfide, and ethylchloroformate resulted in the formation of the new pyrido[4′,3′:4,5]thieno[2,3‐d][1,3,4]thiadiazolo[3,2‐a]pyrimidine derivatives 12–15 . © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:280–286, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10030     

Synthesis of novel pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidines,pyrido[3″,2″:4′,5′]thieno[3′,2′:4,5]pyrimido[l,6‐a]benzimidazoles and related fused systems

3‐Amino‐4‐aryl‐5‐ethoxycarbonyl‐6‐methylthieno[2,3‐b]pyridine‐2‐carboxamides 3a‐c were prepared from ethyl 4‐aryl‐3‐cyano‐6‐methyl‐2‐thioxo‐1,2‐dihydropyridine‐5‐carbonylates 1a‐c and reacted with some carbonyl compounds to give tetrahydropyridothienopyrimidine derivatives 6a‐c, 7a‐c and 8a‐c , respectively. Treatment of compound 3c with chloroacetyl chloride led to the formation of a next key compound, ethyl 2‐chloromethyl‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 9 . Also, 3‐amino‐2‐benzimidazolylthieno[2,3‐b]pyridine‐5‐carboxylate 5 and 2‐(3′‐aminothieno [2,3‐b]pyridin‐2′‐yl)‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 17 were prepared from 1c. The compounds 5, 9 and 17 were used as good synthons for other pyridothienopyrimidines and pyridothienopyrimidobenzimidazoles as well as for related fused polyheterocyclic systems.     

Polycyclic N‐Heterocyclic Compounds. Part 84: Reaction of N‐(pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4‐yl)amidines or N‐(pyrido[2′,3′:4,5]furo[3,2‐d]pyrimidin‐4‐yl)amidines with Hydroxylamine Hydrochloride

The reactions of nine N‐(pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4‐yl)amidines ( 3 ) with hydroxylamine hydrochloride produced new cyclization products. These were formed via ring cleavage of the pyrimidine component followed by a 1,2,4‐oxadiazole‐forming ring closure to give N‐[2‐([1,2,4]oxadiazol‐5‐yl)thieno[2,3‐b]pyridin‐3‐yl]formamide oximes ( 11 ). Reaction of six N‐(pyrido[2′,3′:4,5]furo[3,2‐d]pyrimidin‐4‐yl)amidines ( 12 ) with hydroxylamine hydrochloride gave similar results. Effects of the newly synthesized compounds on pentosidine formation were also evaluated.     

Thieno[2,3‐d]pyrimidines in the Synthesis of New Fused Heterocyclic Compounds of Prospective Antitumor and Antioxidant Agents (Part II)

Diethyl azodicarboxylate and 3,4,5,6‐tetrachloro‐1,2‐benzoquinone react with cyclopentano‐ and cycloheptano‐fused thienopyrimidines to form the oxidative dimer of the starting material via S—S bond formation. Reaction of two equivalents of 2,2′‐(cyclohexa‐2′,5′‐diene‐1,4‐diylidene)dimalononitrile with thienopyrimidines afforded 3‐(4′,4′‐dicyanomethylene‐cycloalka[a]‐2,5‐dienyl)‐4‐oxo‐6,7,8,9‐tetrahydro‐5H‐cyclo‐hepta[4,5]‐[1,3]thiazolo[3,2‐a]‐thieno[2,3‐d]pyrimidin‐2‐ylidene‐2‐dicarbonitriles. The thioenopyrimidines react with 2‐[1,3‐dioxo‐1H‐inden‐2(3H)‐ylidene]malononitrile to produce 1,3,5′‐trioxo‐1,3,3′,5′‐tetrahydrospiro‐(indene‐2,2′‐thiazolo[2,3‐b]‐cycloalkyl[b]‐thieno[2,3‐d]pyrimidine)‐3′‐carbonitriles. However, the reaction of thienopyrimidines with 2,3‐dicyano‐1,4‐naphthoquinone proceeded to afford the fused cycloalkyl‐thieno form of naphtho[1,3]thiazolo[3,2‐a]thieno[2,3‐d]pyrimidine‐6.7,12‐triones. Reaction of 2‐hydrazino‐5,6,7,8‐tetrahydrobenzo[b]thieno[2,3‐d]pyrimidine‐4(1H)‐one with dimethyl acetylenedicarboxylate and ethyl propiolate, respectively, afforded cyclohexano‐fused (Z)‐dimethyl 2[(E)‐4‐oxo‐3,4‐dihydrothieno[2,3‐d]pyrimidine‐2(1H)‐ylidene)hydrazono]succinate and thieno‐pyrimidinotriazine. Both oxidative dimers of thienopyrimidines showed high inhibition of Hep‐G2 cell growth compared with the growth of untreated control cells. Moreover, the cycloheptano‐fused thiazinothienopyrimidine indicates a promising specific antitumor agent against Hep‐G2 cells because its IC₅₀ is < 20 μM.     

Polycyclic N‐Heterocyclic Compounds. Part 81: Synthesis and Evaluation of Pentacyclic 1,2,4,5‐Tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]imidazo[1,2‐c]pyrimidine and Related Compounds as Potential Antiplatelet Aggregators

Dehydrative ring closure reactions were carried out on fused 4‐(2‐hydroxyethylamino) (or 2‐hydroxyethoxy or 2‐hydroxyethylthio)pyrimidines ( 2a , 2b , 2c ) to give fused 2,3‐dihydroimidazo[1,2‐c] (or 2,3‐dihydrooxazolo[3,2‐c] or 2,3‐dihydrothiazolo[3,2‐c])pyrimidines. This reaction produced the pentacyclic 1,2,4,5‐tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]imidazo[1,2‐c]pyrimidine ( 3a ) and 1,2,4,5‐tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]thiazolo[3,2‐c]pyrimidinium chloride ( 3c ) from the 2‐hydroxyethylamino‐derivative and 2‐hydroxyethylthio‐derivative, respectively. In contrast, 2‐hydroxyethoxy‐derivative ( 2b ) gave the rearrangement product, 3‐(2‐chloroethyl)‐5,6‐dihydro[1]benzothieno[3′,2′:2,3]thiepino[4,5‐d]pyrimidin‐4(3H)‐one ( 4 ). Effects of the synthesized compounds on collagen‐induced platelet aggregation were also evaluated.     

Reactions with 3,6‐diaminothieno[2,3‐b]‐pyridines: Synthesis and characterization of several new fused pyridine heterocycles

6‐Aminopyridine‐2(1H)thiones 1 reacting with α‐halo‐compounds 2a–c afforded the alkylthiopyridine derivatives 3a–c which in turn cyclized to the corresponding thieno[2,3‐b]pyridine derivatives 4a–c . Several thieno[2,3‐b]pyridine derivatives 7, 16, 19 , pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine derivatives 6a,b, 11a–c, 21 and pyrido[3′,2′:4,5]thieno[3,2‐c]pyridazine derivatives 13, 17 were prepared starting from compounds 4a–c . © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:405–413, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20313     

Synthesis of Novel Spiro Pyrano[2,3‐d]thiazolo[3,2‐a]pyrimidine via 1,3‐Dipolar Cycloaddition of Azomethine Ylide

The reaction involving 4‐phenyl‐octahydro‐pyrano[2,3‐d]pyrimidine‐2‐thione, ethyl chloroacetate and the appropriate aromatic aldehyde yielded 2‐arylmethylidene‐5‐phenyl‐5a,7,8,9a‐tetrahydro‐5H,6H‐pyrano[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidin‐3(2H)‐ones. The 1,3‐dipolar cycloaddition of 2‐arylmethylidene‐5‐phenyl‐5a,7,8,9a‐tetrahydro‐5H,6H‐pyrano[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidin‐3(2H)‐ones with azomethine ylide generated by a decarboxylative route from sarcosine and acenaphthenequinone afforded 4′‐aryl‐1′‐methyl‐5″‐phenyl‐5a″,7″,8″,9a″‐tetrahydro‐2H,5″H,6″H‐dispiro[acenaphthylene‐1,2′‐pyrrolidine‐3′,2″‐pyrano[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidine]‐2,3″‐diones in moderate yields. The structures of the products were determined and characterized thoroughly by NMR, MS, IR, elemental analysis, and X‐ray crystallographic analysis.     

Synthesis of new heteroaromatic nitrogen ligands: Pyrimido‐[4″,5″:4′,5′]‐thieno[3′,2′:4,5]thieno[3,2‐d]pyrimidines and 1,2,3‐triazine[4″,5″:4′,5′]thieno[3′,2′:4,5]thieno[3,2‐d]‐1,2,3‐triazines

An efficient one‐pot access for the synthesis of the previously unreported tetracyclic fused pyrimido‐[4″,5″:4′,5′]thieno[3′,2′:4,5]thieno[3,2‐d]pyrimidine ( 3 ) and 1,2,3‐triazine[4″,5″:4′,5′]thieno‐[3′,2′:4,5]thieno‐[3,2‐d]‐1,2,3‐triazine ( 5 ) heteroaromatic nitrogen ligands is described. The title compounds 3 and 5 were obtained from 3,4‐diaminothieno[2,3‐b]thiophene‐2,5‐dicarbonitrile and phosgeniminium chloride and sodium nitrite/HCl, respectively. Substituted condensed thieno[2,3‐b]thiophene derivatives 4 and 6 were synthesized by nucleophilic displacement of the chloroderivatives 3 and 5 .     

A convenient synthesis for some new pyrido[3′,2′:4,5]thieno-[3,2-d]pyrimidine derivatives with potential biological activity

Ready, convenient synthesis for 8-cyano-7-ethoxy-4-oxo-9-phenyl-2-substituted-1,2,3,-4-tetrahydropyrido-[3′,2′:,4,5]thieno[3,2-d]pyrimidines 5 , 8-cyano-7-ethoxy-4-oxo-9-phenyl-2-substituted-3,4-dihydropyrido[3′,2-: 4,5]thieno[3,2-d]pyrimidines 6 , 4-chloro-8-cyano-7-ethoxy-9-phenyl-2-substitutedpyrido[3′,2′:4,5]thieno[3,2-4 -pyrimidines 7 and 8-cyano-7-ethoxy-2-(2′-nitrophenyl)-9-phenyl-4-substitutedpyrido[3′,2′:4,5]thieno[3,2- d ]pyrimidines 8-18 from 2-chloro-3,5-dicyano-6-ethoxy-4-phenylpyridine 1 via 3,5-dicyano-6-ethoxy-2-mercapto-4-phenylpyridine 2 and aminocarboxamide 4 are reported. In addition, the reaction of hydrazino derivative 12 with reagents such as formic acid and triethyl orthoformate yielded the fused tetraheterocyclic 8-cyano-9- ethoxy-5-(2′-nitrophenyl)- 7-phenylpyrido[3′,2′:4,5]thieno[2,3-e]-1, 2,4-triazolo[4,3-c]pyrimidine system 19 .     

Synthesis of 3-Substituted Pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines and Related Fused Thiazolo Derivatives

New ethyl 3-(substituted)-4-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydropyrido[4',3':4,5]thieno-[2,3-d]pyrimidine-7-carboxylates ( 3a , b ), ( 6 ),( 11-13 ), ethyl 3-methyl-5-oxo-2,3,6,9-tetrahydro 5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-8(7H)-carboxylate ( 4 ), and ethyl 2-methyl-5-oxo-2,3,6,9-tetrahydro-5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]-pyrimidine-8(7H)-carboxylate ( 8 ) have been synthesized from diethyl 2-isothiocyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate 1. The structure of these compounds as well as their intermediates have been established by their spectral data.     

Utility of Pyridine‐2(1H)‐thiones in the Synthesis of Novel Bis‐Thieno[2,3‐b]pyridines and Their Fused Azines

The starting materials pyridine‐2(1H)‐thiones are prepared and reacted with halogen‐containing reagents in ethanolic sodium acetate solution to give the corresponding 2‐S‐alkylpyridines, which cyclized upon their boiling in methanolic sodium methoxide solution at reflux to give the corresponding thieno[2,3‐b]pyridines in excellent yields. Bis (thieno[2,3‐b]pyridine‐2‐carboxamides), incorporating 2,6‐dibromophenoxy moiety, are prepared by the bis‐O‐alkylation of thieno[2,3‐b]pyridine‐2‐carboxamide derivatives. Two synthetic routes are designed to prepare the target molecules pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4(3H)‐ones, pyrido[3′,2′:4,5]thieno[3,2‐d][1,2,3]triazin‐4(3H)‐ones, and their bis‐analogues using thieno[2,3‐b]pyridine‐2‐carboxamides and their bis‐analogues. The structure of the target molecules is elucidated using elemental analyses as well as spectral data.     

Synthesis and Reactions of the Novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde

The novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde ( 2 ) was efficiently synthesized from Vilsmeier–Haack formylation of 3‐(1‐ethy1‐4‐hydroxy‐2‐oxo‐(1H)‐quinolin‐3‐yl)‐3‐oxopropanoic acid ( 1 ). The aldehyde 2 was allowed to react with some nitrogen nucleophiles producing a variety of hydrazones 3 – 7 . Reaction of aldehyde 2 with hydrazine hydrate and hydroxylamine hydrochloride afforded pyrazole and isoxazole annulated pyrano[3,2‐c]quinoline‐2,5(6H)‐dione, respectively. The reactivity of aldehyde 2 was examined toward some active methylene nitrile, namely, malononitrile, ethyl cyanoacetate, and cyanoacetamide leading to 2‐iminopyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines 10 – 12 , respectively. Also, some novel pyrazolo[4″,3″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines ( 13 , 14 ) and thiazolo[5″,4″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines ( 15 , 16 ) were synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

Synthesis and Reactions of Some New Heterocyclic Compounds Containing Cycloalka[e]thieno[2,3‐b]pyridine Moiety

Hydrolysis of ethyl 3-amino-4-aryl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxylates ( 3a-d) gave the corresponding o-aminocarboxylic acids 4a-d . Heating the latter compounds ( 4a-d) with acetic anhydride furnished the oxazinone derivatives 5a-d which, in turn, underwent recyclization reaction to give the corresponding pyrimidinones 6a-d upon treatment with ammonium acetate in acetic acid. Reaction of 3-amino-4-aryl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxamides ( 3f,h ) with triethyl orthoformate gave pyrimidinone derivatives 7a,b . Reaction of 3-amino-4-phenyl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxamides 3e,h with aromatic aldehydes furnished tetrahydropyridothienopyrimidinones 8a-d . Chlorination of 7a,b and 6a-d by using phosphorous oxychloride produced 4-chlorocycloalka[5′,6′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivatives 9a-f which were used as key intermediates in the synthesis of several new cycloalkapyrido-thienopyrimidines 10a-f ˜ 14a-f . Moreover, some cycloalkapyridothienotriazinones 15a,b-17a,b were synthesized.     

An efficient synthesis of novel pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet–Spengler reaction

An efficient method for the synthesis of novel pyrido[3',2':4',5']thieno[3',2':2,3]pyrido [4,5:d][1,3]thiazolo[3,2-a]pyrimidine-4-one derivatives (5) has been developed using a Pictet-Spengler reaction between 2-(3-aminothieno[2,3-b]pyridin-2-yl)thiazolo[3,2-a] pyrimidin-5-one (3), which could be obtained from the condensation of 7-(chloromethyl)-5H-thiazolo[3,2-a]pyrimidin-5-one (1) with 3-cyanopyridine-2-thione (2) via Thorpe-Ziegler isomerization, and aromatic aldehydes under NH₂SO₃H as catalysis in good yields.     

[1,3]Thiazolo[2′,3′:3,4][1,2,4]triazolo[1,5‐a]pyrimidines – A New Heterocyclic System Accessed via Bromocyclization

A facile access to novel condensed system of [1,3]thiazolo[2′,3′:3,4][1,2,4]triazolo[1,5‐a]pyrimidine is presented. This protocol consists of bromine‐assisted direct electrophilic heterocyclization of 3‐N‐allylamine‐5,6‐dihydro[1,3]thiazolo[2,3‐c][1,2,4]triazole. The bromination took place in acetic acid and gave a good yield of the target product, which was dehydrobrominated by sodium acetate action.     

Ring closure reactions of pyrido[2,3‐d]pyrimidines to pyrano[2′,3′:4,5]‐ and oxazolo[5′,4′:4,5]pyrido[2,3‐d]pyrimidines

The cyclocondensation of 5‐hydroxy‐pyrido[2,3‐d]pyrimidines 1 with malonates gives pyrano[2′,3′:4,5]‐pyrido[2,3‐d]pyrimidines 2 . Nitration of 1 and reduction with zinc in the presence of carboxylic acids/anhydrides gave 2‐alkyloxazolo[5′,4′:4,5]pyrido[2,3‐d]pyrimidines 4 , which were ring‐opened to 6‐aminopyrido[2,3‐d]pyrimidines 5, 6 and 7 . Cyclization of 6‐aminopyrido[2,3‐d]pyrimidines 6 with benzoylchlorides 8 gave 2‐aryloxazolo[5′,4′:4,5]pyrido[2,3‐d]pyrimidines 9 . Reaction conditions for the cyclization have been studied by differential scanning calorimetry (DSC).     

A Catalyst‐Free Aqueous Synthesis of 2‐Amino‐7,9‐dihydrothieno[3′,2′:5,6]pyrido[2,3‐d]pyrimidine‐4,6(3H,5H)‐dione Derivatives

A series of novel 7,9‐dihydrothieno[3′,2′:5,6]pyrido[2,3‐d]pyrimidine‐4,6(3H,5H)‐dione derivatives were synthesized efficiently via the catalyst‐free reaction of aldehyde, ethyl 2,4‐dioxotetrahydrothiophene‐3‐carboxylate, and 2,6‐diaminopyrimidine‐4(3H)‐one through the sequence of deethoxycarbonylation and three‐component condensation in aqueous media. This protocol featured mild reaction conditions, high yields, easy work‐up, and environmentally friendly procedure.     

Synthesis,Characterization and Reactions of 4‐Hydrazino‐2‐methylpyrimidino[4′5′:4,5]thiazolo[3,2‐a]benzimidazole

4‐Hydrazino‐2‐methylpyrimidino[4′,5′:4,5]thiazolo[3,2‐a]benzimidazole ( 4 ) was obtained from hydrazinolysis of the 4‐chloro derivative 3 with hydrazine hydrate. The hydrazino derivative 4 was further cyclized to the corresponding pyrazole 5 , pyrazolone 6 and 5‐methyl‐1,2,4‐triazolo[1″,5″:3′,4′]pyrimidino[5′,6′:5,4]‐thiazolo[3,2‐a]benzimidazole ( 9 ) and 5‐methy‐1,2,4‐triazolo[4″,3″:3′,4′]pyrimidino[5′,6′:5,4]thiazolo‐[3,2‐a]benzimidazole ( 10 ), respectively. The triazolo derivative 10 was isomerized to the triazolo derivative 9 under a variety of reaction conditions.     

Synthesis of Novel Pyridothienopyrimidines,Pyridothienopyrimidothiazines, Pyridothienopyrimidobenzthiazoles and Triazolopyridothienopyrimidines

The reaction of 3‐amino‐4,6‐dimethylthieno[2,3‐b]pyridine‐2‐carboxamide (1a) or its N‐aryl derivatives 1b‐d with carbon disulphide gave the pyridothienopyrimidines 2a‐d , whilst when the same reaction was carried out using N¹‐arylidene‐3‐amino‐4,6‐dimethylthieno[2,3‐b]pyridine‐2‐carbohydrazides (1e‐h) , pyridothienothiazine 3 was obtained. Also, refluxing of 1b‐d with acetic anhydride afforded oxazinone derivative 4 . Compounds 2a and 2b‐d were also obtained by the treatment of thiazine 3 with ammonium acetate or aromatic amines, respectively. When compound 2a was allowed to react with arylidene malononitriles or ethyl α‐cyanocinnamate, novel pyrido[3″,2″:4′,5′]thieno[3′,2′:4,5]pyrimido[2,1‐b][1,3] thiazines 5a‐c were obtained. Treatment of 2b‐d with bromine in acetic acid furnished the disulphide derivatives 6a‐c . U.V. irradiation of 2b‐d resulted in the formation of pyrido[3″,2″:4′,5′]thieno[3′,2′:4,5]pyrimido[2,1‐b]benzthiazoles 7a‐c . The reaction of 2a‐d with some halocarbonyl compounds afforded the corresponding S‐substituted thiopyrido thienopyrimidines 8a‐j . Compound 8b was readily cyclized into the corresponding thiazolo[3″,2″‐a]‐pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine 9 upon treatment with conc. sulphuric acid. Heating of 2a,b with hydrazine hydrate in pyridine afforded the hydrazino derivatives 11a,b . Reaction of ester 8c with hydrazine hydrate in ethanol gave acethydrazide 10 . Compounds 10 and 11a,b were used as versatile synthons for other new pyridothienopyrimidines 12–15 as well as [1,2,4] triazolopyridothienopyrimidines 16–19.     

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.