Mohamed A. M. Gad-Elkareem

Thieno[2,3-b]pyridine-2-carbohydrazide in Polyheterocyclic Synthesis: The Synthesis of Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine, Pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine, and Pyrazolyl, Oxadiazolylthieno[2,3-b]pyridine Derivatives

Pyrdine-2(1H)-thione 1 reacted with ethyl chloroacetate 2 to give 2-S-ethoxy-carbonylmethylpyridine derivative 3, which could be cyclized into thieno[2,3-b]-pyridine-2-carbohydrazide derivative 5 by boiling with hydrazine hydrate. The latter compound reacted with cinnamonitrile derivatives 6a, b, triethylorthoformate, formic acid, dimethylformamide-dimethylacetal, and diethyl carbonate to give the corresponding shiff base 7a, b and pyrido[3′,2′;-4,5]thieno[3,2-d]pyrimidine derivatives 10–13 in respective manner. On the other hand, compound 5 also reacted with carbondisulphide and phenyl isothiocyanate to afford the corresponding 2-(1,3,4-oxadiazolo-2-yl)thieno[2,3-b]pyridine derivatives 18 and 22. Finally, compound 5 reacted with some β-dicarbonyl compounds, such as ethyl acetoacetate, acetylacetone and ethyl β-arylazoacetoacetate, to yield the corresponding 2-(pyrazol-1-yl-carbonyl)thieno[2,3-b]pyridine derivatives 24, 25, and 27 respectively.

Pyrido[2,3-d]pyrimidine-2,7-dithiol in heterocyclic synthesis: Synthesis and characterization of several new fused pyridopyrimidine heterocycles

Pyridine-2(1H)-thione 1 reacted with phenyl isothiocyanate to give pyrido[2,3-d]pyrimidine derivative 3. Compound 3 reacted with halogen containing compounds 4a–d and methyl iodide in dimethylformamide/potassium hydroxide solution at room temperature to give 2,7-bisalkylthiopyrido[2,3-b]pyrimidine derivatives 5a–d and 9, respectively. Compounds 5a–d could be cyclized into thienopyrido[2,3-d]pyrimidine derivatives 6a–d by boiling with ethanolic potassium hydroxide solution. Compound 6a reacted with acetic anhydride or formic acid and gave the corresponding pyrimido[4″,5″:4′,5′]thieno[3′,2′:5,6]pyrido[2,3-d]pyrimidine derivatives 8a,b. Compound 9 reacted with hydrazine hydrate to yield pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine derivative 11 which could be reacted with nitrous acid and dimethylformamide-dimethylacetal (DMF-DMA) and gave the final isolable products corresponding to the pyrazolo[4′,3′:5,6]pyrido[2,3-d]tetrazolo-[5,1-b]pyrimidine and pyrimido[1″,2″:1′,5′]pyrazolo[4′,3′:5,6]pyrido[2,3-d]1 2 4triazolo-[4,3-b] pyrimidine derivatives 13 and 17, respectively. Compound 11 also reacted with some β-dicarbonyl compounds such as acetylacetone (18) and ethyl acetoacetate (20) to yield the corresponding pyrimido[1″,2″:1′,5′]pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine derivatives 19 and 21, respectively. Finally, compound 11 reacted with chloroacetyl chloride (22) to give the corresponding imidazo[1″′,2″′:1″,5″]pyrazolo[4″,3″:5′,6′]pyrido[3′,2′:5,6]pyrimido[2,1-c]1 2 4triazine derivative 23.

A Novel Synthesis of Pyridine-2(1H)-thione, Pyrazolo[3,4-b]pyridine, Pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine, Thieno[2,3-b]pyrdine, and Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine Derivatives Containing a Naphthyl Moiety

6-Amino-4-naphthyl-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitriles 3a, b were synthesized from the reaction of naphthaldehydes 1a, b and cyanothioacetamide (2). Compounds 3a, b were taken as starting materials for the synthesis of pyrazolo[3,4-b]pyridine 7a, b, and 8a, Pyrido-[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine 9a, b; thieno[2,3-b]pyridine 16a–d, 18a, b, 21a–d, 24a, b, and 25a; and pyrido[3,2:4,5]thieno[3,2-d]pyrimidine 17a, b derivatives through their reactions with the corresponding reagents. All structures of the newly synthesized heterocyclic compounds were established on the basis of IR, 1H NMR, 13C NMR, mass spectra, and elemental analyses.

Pyridine-2(1H)-thione in Heterocyclic Synthesis: Synthesis of Some New Nicotinic Acid Ester, Thieno[2, 3-b]pyridine, Pyrido[3′, 2′: 4, 5]thieno [3, 2-d]pyrimidine, and Thiazolylpyrazolo[3, 4-b]pyridine Derivatives

Nicotinic acid esters 3a–c were prepared by the reaction of pyridine-2(1H)-thione derivative 1 with α-halo-reagents 2a–c. Compounds 3a–c underwent cyclization to the corresponding thieno[2, 3-b]pyridines 4a–c via boiling in ethanol/piperidine solution. Compounds 4a–c condensed with dimethylformamide-dimethylacetal (DMF-DMA) to afford 3-{[(N,N-dimethylamino)methylene]amino}thieno[2, 3-b]- pyridine derivatives 6a–c. Moreover, compounds 4a–c and 6a–c reacted with different reagents and afforded the pyrido[3′,2′:4, 5]thieno[3, 2-d]pyrimidine derivatives 10a–d, 11a–c, 12a,b, 14a,b, 17, and 19. In addition, pyrazolo[3, 4-b]pyridine derivative 20 (formed via the reaction of 1 with hydrazine hydrate) reacted with ethylisothiocyanate yielded the thiourea derivative 21. Compound 21 reacted with α-halocarbonyl compounds to give the 3-[(3H-thiazol-2-ylidene)amino]-1H-pyrazolo[3, 4-b]pyridine derivatives 23a–c, 25, and 27a,b.

N-1-Naphthyl-3-oxobutanamide in Heterocyclic Synthesis: A Facile Synthesis of Nicotinamide, Thieno[2,3-b]pyridine, and Bi- or Tricyclic Annulated Pyridine Derivatives Containing Naphthyl Moiety

N-1-Naphthyl-3-oxobutanamide (1) reacts with arylidinecyanothioacetamide 2a–c in ethanol/piperidine solution under reflux to yield the pyridine-2(1H)-thiones 6a–c. Compound 6a reacts with α-haloketones 7a–e to give the 6-thio-N-1-naphthyl-nicotinamides derivatives 8a–e, which cyclized to thieno[2,3-b]pyridine derivatives 9a–e. The reaction of compound 9a with hydrazine hydrate and formamide gives the thieno[2,3-b]pyridine carbohydrazide derivative 10 and pyridothienopyrimidine derivative 11, respectively. Reaction of 9a with benzoyl isothiocyanate gave thiourea derivative 12. Compound 12, upon treatment with alcoholic NaOH, gave pyridothienopyrimidine 13. Saponifications of 9a gave the amino acid 15, which affords 16 when refluxed in Ac2O. Treatment of compound 16 with AcONH4/AcOH gave 17. Diazotization and self-coupling of 9b gave the pyridothienotriazine 18. Also, diazotization of the ortho-aminohydrazide 10 give the corresponding azide 19, which was subjected to Curtius rearrangement in boiling xylene to give imidazothienopyridine 20. Reaction of 10 with either formic acid or triethylorthoformate and phenyl isothiocyanate gave the corresponding pyridothienotriazepines 22 and 23, respectively. The interaction of 10 with acetylacetone furnished the pyrazolyl derivative 24. The structures of the synthesized compounds were established from their analytical and spectral data.

Pyridine-2(1H)-thione in heterocyclic synthesis: synthesis and antimicrobial activity of some new thio-substituted ethyl nicotinate, thieno[2,3-b]pyridine and pyridothienopyrimidine derivatives

3-(4-Bromophenyl)-2-cyanoprop-2-enethioamide (1) reacted with ethyl 3-oxo-3-phenylpropanoate (2) to give ethyl 4-(4-bromophenyl)-5-cyano-2-phenyl-6-thioxo-1,6-dihydropyridine-3-carboxylate (3). Compound 3 was taken as a starting material for the synthesis of thio-substituted ethyl nicotinate derivatives 5a–d, which underwent cyclization to the corresponding thieno[2,3-b]pyridines 6a–d. Also 3 reacted with hydrazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 7, which upon diazotization gave the diazonium derivative 8. Compound 6a condensed with dimethylformamide–dimethylacetal to afford thieno[2,3-b]pyridine derivative 9, which reacted with different amines 10a–e to afford the pyridothienopyrimidine derivatives 12a–e through the Dimroth rearrangement. Moreover, compound 6a reacted with different reagents to give pyridothienopyrimidine derivatives 14a and b, 17 and pyrazolothienopyridine derivative 18. In addition, acetylating compound 6c with chloroacetylchloride afforded the 3-[(2)-chloroacetylamino]thieno[2,3-b]pyridine derivative 20, which upon cyclization yielded the corresponding 2-chloromethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivative 21. Some of the newly synthesized compounds were screened in vitro for their antimicrobial activities.

Synthesis and Antibacterial Activity of Some New Ethyl Thionicotinates, Thieno[2,3-b]pyridines, Pyrido[3′,2′:4,5] thieno[3,2-d]pyrimidines, and Pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazines Containing Sulfonamide Moieties

Ethyl 5-cyano-6-mercaptonicotinate derivatives 1a,b reacted with the N-[4-(aminosulfonyl) phenyl]-2-chloroacetamide derivatives 2a,b to give the ethyl 6-[(2-{[4-(aminosulfonyl) phenyl]amino}-2-oxoethyl)thio]nicotinate derivatives 3a–d. Cyclization of 3a–d afforded the corresponding ethyl 3-amino-2-({[4-(aminosulfonyl)phenyl]amino}carbonylthieno[2,3-b] pyridine-5-carboxylate derivatives 4a–d. Ethyl 3-[4-(amino-sulfonyl)phenyl]-4-oxopyrido [3′,2′:4,5]thieno[3,2-d]pyrimidine-8-carboxylate derivatives 5a–d and ethyl 3-[4-(amino- sulfonyl)phenyl]-4-oxopyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]-triazine-8-carboxylate derivat- ives 6a–d were prepared from 4a–d. Reaction of 1a,b with chloroacetonitrile (7) and condensation of the thus formed 3-aminothienopyridines 8a,b with dimethylformamide-dimethylacetal (DMF-DMA) yielded the corresponding ethyl 2-cyano-3-{[(N, N-dimethylamino)methylene]amino}thieno[2,3-b]pyridine-5-carboxylate derivatives 9a,b. Reaction of compounds 9a,b with the sulfadiazine (10) gave ethyl 4-{[4-(amino- sulfonyl)phenyl]amino}pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-8-carboxylate derivatives 12a,b. Antibacterial activity was screened for some of the newly synthesized compounds. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.