الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 173 |  |  |
| | | from | 173 | | |
Abstract
Reaction of 305 with diethylmalonate in bromobenzene under reflux afforded 2-ethylthio-1,5-dihydro-7-hydroxy-5-oxo-1-phenyl-1,2,4-triazolo[1,5-a]pyridine-8-carbonitrile (306). Reacting 306 with Vilsmeir-Haack reagent derived from phosphorus oxychloride-dimethylformamide at 65-70oC for 6 hours lead directly to 7-chloro-6-formyl-1,2,4-triazolo[1,5-a]pyridine derivative 308, instate of 307. Treatment of 308 with an equimolar amount of [(ethoxycarbonyl)methylene] triphenylphosphorane (309) in CHCl3 at room temperature gave 7-chloro-6-ethoxycarbonylvinyl-2-ethylthio-1,5-dihydro-5-oxo-1-phenyl-1,2,4-triazolo[1,5-a]pyridine-8-carbonitrile (310). The structure of 310 was substantiated by its elemental analysis and spectral data (IR, 1H, 13C NMR and MS). Analytical data was also in accordance with the proposed structure. Additionally, the structure of 310 was unambiguously confirmed by X-ray crystallography. Azidation of 310 with sodium azide in DMF at room temperature gave the corresponding 7-azidotriazolopyridine derivatives 311.
The 7-azido-1,2,4-triazolo[1,5-a]pyridine derivatives 311 was used as a model compound for studying all the reactions leading to the construction of novel tricyclic systems incorporating a triazole nucleus in addition to naphthyridine moiety. Thus, reduction of the azide moiety in 311 with Na2S2O4 furnished the corresponding 7-aminotriazolopyridines 312. The amino compound 312 was heated in DMF under reflux, an intramolecular cyclization took place and lead directly to the previously unknown ring system 2-ethylthio-1,5,8,9-tetrahydro-5,8-dioxo-1-phenyl-1,2,4-triazolo[1,5-g][1,6]naphthyridine-10-carbonitrile (313), in fair yield (62%).
On the other hand, treatment of iminophosphorane 314 with phenyl isothiocyanate in refluxing 1,2-dichlorobenzene for 4 hours gave the novel ethyl-10-cyano-2-ethylthio-1,5-dihydro-5-oxo-1-phenyl-8-(phenylamino)-1,2,4-triazolo-[1,5-g][1,6]naphthyridine-7-carboxylate (318) in 86% yield (Scheme 96). The formation of tricyclic system 318 can be explained by an initial aza-Wittig-type reaction between the iminophosphorane group directly linked to the heterocyclic ring and 1.25 equiv. of the phenyl isothiocyanate to give carbodiimide 316, which undergoes intramolecular cyclization to yield a further intermediate 317 which then undergoes a proton shift to afford the final product 318
On the other hand, refluxing compound 310 with an excess of alkyl amines namely, isobutyl and n-butyl amine 319a,b in abs. EtOH for 6 hours gave in each case the corresponding 7-alkylamino-1,2,4-triazolo[1,5-a]pyridines 320a,b. respectively. When compounds 320a,b were heated in DMF under reflux, an intramolecular heterocyclization across the electrophilic ester functionality was occurred to give the fused tricyclic systems 321a,b, namely 9-alkyl-2-ethylthio-1,5,8,9-tetrahydro-5,8-dioxo-1-phenyl-1,2,4-triazolo[1,5-g][1,6]naphthyridine-10-carbonitriles, as new model system for 1,2,4-triazolonaphthyridines (Scheme 97). from these results, we concluded that intramolecular cyclocondensation between the amino and ester groups in 320a,b occurred with the formation of the first example of a linear, annulated 1,2,4-triazolo[1,5-g][1,6]naphthyridines.
On the other hand, reduction of the azido group in 326 with Na2S2O4 in (MeOH / H2O) gave the corresponding 7-amino-1,2,4-triazolo[1,5-a]pyridine 328. We invisaged that the thermal cyclization of 328 in boiling bromobenzene might afford the hitherto unknown tricyclic pyrazolotriazolopyridines 329. Interestingly, however, an unexpected new compound, 7amino-1,2,4-triazolo[1,5-a]pyridine-6,8-dicarbonitriles 330, which was obtained
Treatment of oxime 325 with POCl3 afforded the corresponding 7-cloro-1,2,4-triazolo[1,5-a]pyridine-6,8-dicarbonitriles 331. which was followed by treatment of excess of sodium azide in DMF at room temperature to yield the corresponding azido compound 332. When this compound was treated with Na2S2O4 in MeOH/H2O (2:1) mixture at room temperature to afford the corresponding 7-amino-1,2,4-triazolo[1,5-a]pyridines 330
Reaction of 7-chloro-1,2,4-triazolo[1,5-a]pyridine derivatives 308 with an excess of alkyl amines namely,isobutyl, isobutyl and 3-pyridyl 319a-c in abs. EtOH, containing a catalytic amount of AcOH, at room temperature afforded the corresponding new aminoaldehyde 337a-c respectively (Scheme 105).
These obtained amines 337a-c reacted with ethyl cyanoacetate in an ethanolic solution containing piperidine did not give one of the expected tricyclic compounds 338 or 339, but instead, the 2-cyano-3-(8-cyano-2-ethylthio-5-oxo-1-phenyl-7-piperidino-1,5-dihydro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-acrylic acid ethyl ester (340) was obtained as new derivative of 1,2,4-triazolo[1,5-a]pyridine
When compound 308 was allowed to react with aryl amine aniline, p-methoxy aniline and p-methyl aniline 343a-c in boiling ethanol give the interesting benzo[b][1,2,4-triazolo[1,5-g][1,6]naphthyridines 344a-d. On the other hand, reaction of 308 with 343a under the same reaction condition as used for the synthesis of 337, gave compound 346a, which under went interamolecular condensation in EtOH, containing a catalytic amount of acetic acid, under reflux to give 344a (Scheme 108). On the other hand, treatment of 308 with hydrazines namely hydrazine hydrate (80%) and phenyl hydrazine 347a,b furnished the previously unknown ring systems pyrazolo[3,4-d][1,2,4-triazolo[1,5-a]pyridines 348 and 350 respectively. The latter under went intramolecular condensation in boiling acetic acid to give the novel tricyclic system 351