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 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. 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 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.     

Synthesis of two novel ring systems via photocyclization: Thieno[2′,3′:4,5]thieno[2,3-c][1,10]phenanthroline and thieno[3′,2′:4,5]thieno[2,3-c][1,10]phenanthroline

The synthesis of thieno[2′,3′:4,5]thieno[2,3-c][1,10]phenanthroline ( 5 ) and thieno[3′,2′:4,5]thieno-[2,3-c][1,10]phenanthroline ( 10 ) are described. Each compound was obtained in four steps from known starting materials. The basic skeleton of the molecule and of the phenanthroline ring were formed via photocyclization. The total assignment of ¹H-nmr spectra was accomplished with the aid of two-dimensional nmr methods.     

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.     

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.     

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.     

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.     

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.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 13. Dibenzo-[f,h]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline

The synthesis of a previously unknown polycyclic heterocyclic ring system, dibenzo[f,h]phenanthro-[9′,10′:4,5]thieno[2,3-c]quinoline ( 4 ), was accomplished via photocyclization of the appropriate amide followed by chlorination. Substitution of the chlorine atom with hydrazine followed by removal of the hydrazine moiety with 10% copper sulfate solution afforded the parent ring system 4 . The unequivocal assignment of its highly congested ¹H and ¹³C spectra was accomplished by utilizing two-dimensional nmr methods.     

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyrimido[4′,5′:4,5]theino[2,3-b]quinoline and pyrido[1′,2′:1,2]pyrimido[4,5-b]quinoline

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyriraido[4′,5′:4,5]theino[2,3-b]quinoline and 12-phenylpyrido[1′,2′:1,2[pyrimido[4,5-b]quinoline are 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 .     

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.     

Quino[1,2-c]quinazolines. I. Synthesis of quino[1,2-c]quinazolinium derivatives and the related indazolo[2,3-a]quinoline derivatives as analogs of the antitumor benzo[c]phenanthridine alkaloids

9,10-Dimethoxy-1,2,3,4,12,13-hexahydro-1-oxoquino[1,2-c]quinazolinium perchlorate, 1,2,3,4,13,24-hexahydro-1-oxo[1,3]dioxolo[4,5-g]quino[1,2-c]quinazolinium perchlorate, 6-methyl-2,3,9,10-tetramethoxyquino-[1,2-c]quinazolinium perchlorate and 2,3-dimethoxy-13-methyl[1,3]dioxolo[4′,5′:6,7]quino[1,2-c]quinazolinium perchlorate were synthesized as analogs of the potent antitumor benzo[c]phenanthridine alkaloids nitidine and fagaronine. The related 2,3,8,9-tetramethoxyindazolo[2,3-a]quinoline and 2,3-dimethoxy[1,3]dioxolo-[4,5-g]indazolo[2,3-a]quinoline were also synthesized. Further, the novel formation of 6,7-dimethoxy-2-(2-ethylamino-4,5-dimethoxyphenyl)quinoline via reductive alkylation with Raney nickel in refluxing ethanol is also reported.