Synthesis and total 1H-NMR assignment of naphtho[1′,2′:4,5]thieno[2,3-c][1,10]phenanthroline and naphtho[2′,1′:4,5]-thieno[2,3-c] [1,10]phenanthroline

Naphtho[1′,2′:4,5]thieno[2,3-c][1,10]phenanthroline and naphtho[2′,1′:4,5]thieno[2,3-c][1,10]phenanthroline, two novel polycyclic heterocyclic ring systems, have been synthesized in four steps from known starting materials. The total ¹H nmr spectral assignments were made using a COSY experiment to identify the spin systems.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 1. Thieno[3′,2′:4,5]thieno[2,3-c]quinoline and thieno[2′,3′:4,5]thieno[2,3-c]quinoline

The synthesis of two previously unknown heterocyclic ring systems, namely, thieno[3′,2′:4,5]thieno[2,3-c]-quinoline and thieno[2′,3′:4,5]thieno[2,3-c]quinoline is reported. These two novel ring systems were assembled by photocyclization of the appropriate anilides.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 4 . Benzo[f]thieno[2′,3′:4,5]thieno[2,3-c]quinoline and Benzo[h]thieno[2′,3′:4,5]thieno[2,3-c]quinoline and the total assignment of their 1H- and 13C-NMR spectra

The synthesis of two novel polycyclic heterocyclic ring systems via photocyclization are reported. These are benzo[f]thieno[2′,3′:4,5]thieno[2,3-c]quinoline and benzo[A]thieno-[2′,3′:4,5]thieno[2,3-c]quinoline. The total assignment of their ¹H- and ¹³C-nmr spectra was determined by utilizing two-dimensional nmr spectroscopic methods.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 9. Phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,and benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline

The synthesis of three novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 13 ), benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 14 ), and benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 15 ).     

The synthesis of novel polycyclic heterocyclic ring system via photocyclization. 18. Benzo[h]naphtho-[1′,2′:4,5]thieno[2,3-c]quinoline and benzo[h]naphtho-[1′,2′:4,5]thieno[2,3-c] [1,2,4]triazolo[4,3-a]quinoline

The synthesis of two previously unknown polycyclic ring systems, benzo[h]naphtho[1′2′:4,5]-thieno[2,3-c]quinoline ( 1 ) and benzo[h]naphtho[1′,2′:4,5]thieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline ( 2 ), was achieved via oxidative photocyclization of 1-chloro-N-(1-naphthyl)naphtho[2,1-b]thiophene-2-carboxamide ( 5 ). The total assignment of their ¹H and ¹³C nmr spectra was determined by the concerted use of two-dimensional nmr methods.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 19. Thieno[3′,2′:4,5]thieno[2,3-c]-naphtho[1,2-f]quinoline,thieno[3′,2′:4,5]thieno[2,3-c]naphtho-[1,2-f][1,2,4]triazolo[4,3-a]quinoline and thieno[3′,2′:4,5]-thieno[2,3-c]naphtho[1,2-f]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-(3-phenanthryl)thieno[2,3-b]thiophene-2-carboxamide ( 5 ) yielded only one of the two possible structural isomers, thieno[3′,2′:4,5]thieno[2,3-c]naphtho[1,2-f]quinolin-6(5H)-one ( 6 ), which was further elaborated to afford the unsubstituted ring system 10 , its triazole 11 and tetrazole 12 . The structural confirmation of 10 was achieved by the total assignment of its ¹H and ¹³C nmr spectra by the concerted utilization of two-dimensional nmr spectroscopic methods.     

The synthesis of monomethoxynaphtho[1′,2′:4,5]thieno[2,3-c]quinolines

A series of monomethoxynaphtho[1′,2′:4,5]thieno[2,3-c]quinolines has been prepared by photocyclization of the appropriate N-methoxyphenyl-1-chloronaphtho[2,1-b]thiophene-2-carboxamides. Some of the lactams obtained were converted into the thiolactams and their S-methyl derivatives. The lactams were also converted into the corresponding 6-chloro derivatives. Some of these were catalytically dechlorinated into the monomethoxynaphtho[1′,2′:4,5]thieno[2,3-c]quinolines which were then quaternized into the N-methyl quaternary salts.     

The Synthesis of Novel Polycyclic Heterocyclic Ring Systems via Photocyclization. 12. Benzo[h]naphtho-[2′,1′:4,5]thieno[2,3-c]quinoline and benzo[f]-naphtho[2′,1′:4,5]thieno[2,3-c]quinoline

The synthesis of two previously unknown heterocyclic ring systems, namely benzo[h]naphtho[2′,1′:4,5]thi-eno[2,3-c]quinoline (1) and benzo[f]naphtho[2′,1:4,5]thieno[2,3-c]quinoline (2) was accomplished via photocyclization of the appropriate amides followed by chlorination and catalytic dechlorination. The total assignment of ¹H and ¹³C nmr spectra of 2 was determined utilizing two-dimensional nmr methods, providing unequivocal structural proof of the two novel polycyclic ring systems.     

The synthesis of novel polycyclic heterocyclic ring systems. 3. Synthesis and NMR spectroscopy of 15-chloro[1]benzo-thieno[2″,3″:3′,4′]naphtho[1′,2′:4,5]thieno[2,3-c]quinoline

The polycyclic heterocyclic compound with a novel ring system, 15-chloro[1]benzothieno[2″,3″:3′,4′]-naphtho[1′,2′:4,5]thieno[2,3-c]quinoline was synthesized via photocyclization of 3-chloro-N-phenyl[1]-benzothieno[2′,3′:3,4]naphtho[2,1-b]fhiophene-2-carboxamide followed by chlorination with phosphorus oxychloride. The assignment of its ¹H and ¹³C nmr spectra was accomplished by utilizing two-dimensional nmr methods.     

Fusions of pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines with N-heterocyclic moieties

Versatile 2-thioxopyrimidine-type building blocks ethyl 3-(2-ethoxy-2-oxoethyl)- 4 -oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidine-7-carboxylate ( 4 ) and ethyl 4-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidine-7-carboxylate ( 8 ) were synthesized from diethyl 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate ( 1 ). Derivatives of linear and angular heterocyclic systems having the imidazole and 1,2,4-triazole ring were obtained from the key intermediates 4 and 8 , respectively.     

Polyazasteroids II.. 1,2,4-Triazolol[3′,4′:2,3]pyrimido[4,5-c]quinolin- 11(12H)ones,imidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3] pyrimido[4,5-c]quinolin-11(12H)ones

Starting with 2-substituted quinoline-3,4-dicarboxylic acids, a series of substituted 1,2,3,4-tetrahydropyrimido[4,5-c]quinolinone-3-thiones were obtained. The latter compounds were converted to the three novel polyazasteroid series: 1,2,4-Triazolo[3′,4′:2,3]pyrimido[4,5-c]-quinolin-11(12H)ones, imidazo[2′,1′:2,3]pyrimido[4,5c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones. The intermediate 3-hydrazino-1,2-dihydropyrimido[4,5-c]quinolinones and nitrous acid gave the 3-azido derivatives rather than the tetrazolo compounds.     

Synthesis of some pyrimido[4′,5′:4,5]thieno[2,3-b]quinolines and related heterocycles

Several thieno[2,3-b]quinolines 6a-i have been synthesized. These compounds were used as key intermediates in the synthesis of oxazino[4′,5′:4,5]thieno[2,3-b]quinoline 8 , pyrimido[4′,5′:4,5]-thieno[2,3-b]quinolines 9–12 , triazino[4′,5′:4,5]thieno[2,3-b] quinolines 14 and imidazo[4′,5′:4,5]-thieno[2,3-b]quinolines 17 .     

Synthesis of the isomeric monomethyl derivatives of the novel naphtho[2′,1′:4,5]thieno[2,3-c]quinoline ring system

The synthesis of the novel naphtho[2′,1′:4,5]thieno[2,3-c]quinoline (11) ring system and four of the isomeric monomethyl derivatives is described.     

Studies of thieno[2,3-b]pyrazines in preparation of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidines and related molecules

A variety of 2,3-disubstituted derivatives of the previously unknown thieno[2,3-b]pyrazine ring system have been employed as a synthetic foundation for pyrazino[2′,3′:4,5]thieno[3,2-d]-pyrimidine and several of its derivatives.     

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 .     

New polyheterocyclic series based on 4,5,6,7-tetrahydrothieno[2,3-c]pyridine

4,8-Dimethyl-6,7,8,9-tetrahydropyrido[4′,3′:4,5]thieno[2,3-e][1,2,4]triazolo[3,4-a]-4H-pyrimidin-5-ones, 7-methyl-2,3,6,7,8,9-hexahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrrolo[1,2-a]-1H, 10H-pyrimidin-10-one, 8-methyl-1,2,3,4,7,8,9,10-octahydropyrido[4′,3′:4,5]thieno[2,3-d]-11H-pyrimidin-11-one, and 9-methyl-2,3,4,5,8,9,10,11-octahydro[4′,3′:4,5]thieno[2,3-d]azepino-[1,2-a]-1H, 12H-pyrimidin-12-one which consist four new heterocyclic ring systems were synthesized from 2-amino-3-carbethoxy-5-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine.     

Synthesis and S-methylation of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-d]-pyrimidin-4(3H)-ones with and without a phase transfer catalyst

A number of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-H]pyrimdin-4(3H-ones (5) have been synthesized by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-b]pyridines (3) with various isothiocyanates. Compounds 5 were S-methylated routinely and the reactions compared under solid-liquid phase transfer conditions to obtain 2-methylthiopyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-^ones (6). The new triheterocyclic pyridothienopyrimidines were prepared with the objective to study their pharmacological properties.     

Pyrido[2′1′:2,3]imidazo[4,5-c]isoquinoline and the alkylation of pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one

The reaction of 2-aminopyridine, o-phthaldehydic acid and potassium cyanide gave pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one, which upon treatment with propargylbromide, yielded both O and N alkylated products. 2-Aminopyridine, o-phthaldehyde and potassium cyanide gave 1-cyano-2-(2-pyridyl)isoindole which rearranged in acid to give the previously unreported parent pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinole. Structures were confirmed using uv, ir, nmr and x-ray spectroscopy.     

Synthesis of 3‐substituted pyrido[4′,3′:4,5]thieno[2,3‐d]pyrimidines and related fused thiazolo derivatives

Convenient syntheses of 3‐substituted ethyl 4‐oxo‐2‐thioxo‐1,2,3,4,5,6,7,8‐octahydropyrid[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‐5H‐pyrido[4′,3′:4,5]thieno[2, 3‐d][1,3]thiazolo[3,2‐a]pyrimidine‐8[7H]carboxylate ( 8 ) from diethyl 2‐isothiocyanato‐4,5,6,7‐tetrahythieno[2,3‐c]pyridine‐3,6‐dicarboxylate ( 1 ) are reported. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:201–207, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10131     

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