The dissertation is devoted to novel approaches towards the synthesis of heterocyclic systems of imidazo[1,2-a]quinolin-5-one, pyrrolo- and imidazo[1,2-a]quinazolin-5-ones from anthranilic acid amides and alkylisatoic anhydrides, as well as heterocyclizations of aminoacrylates. Synthetic transformations relied on using polyfunctional compounds in heterocyclizations, "domino" reactions and multistage "one-pot" transformations, which provided an access to previously unknown derivatives of imidazo[1,2-a]quinolin-5-one, pyrrolo- and imidazo[1,2-a]quinazolin-5 one, as well as 4-fluoroalkyloxazole-5-carboxylic acids.
The reaction of functionalized N-alkylisatoic anhydrides with methylene active carbonitriles was applied for the preparation of imidazo[1,2 a]quinoline derivatives via the "domino" reaction. The common procedure included using sodium acetate in acetic acid and resulted in formation of imidazo[1,2-a]quinoline-2,5-(1H,3H)-dions and imidazo¬[1,2 a]¬quinoline-5(3H)-ones with a nitrile group, as well as heterocycles bearing benzothiazol-2-yl, (N-methyl)benzimidazol-2-yl, and (4 chloro¬phenyl)thiazol-2-yl substituents in 4-position of the heterocyclic system. In turn, using triethylamine in DMF or 1,4-dioxane allowed the synthesis of the corresponding intermediates, which were also applied as an evidence of the mechanism of this transformations.
It was found that N-alkylisatoic anhydride with an additional electrophilic functional group at the alkyl substituent are suitable starting materials for "domino" reactions. However, the activity of an additional electrophilic group should be lower than that of carbonyl group of benzoxazine cycle for an unambiguous process. Among the studied isatic anhydrides, derivatives alkylated with α-chloroethyl acetate and α-chloropinacoline were found to be suitable for succesfull transformatiosn. However, the activity of keto group of the N-acetonyl derivative was excessive and sometimes led to the formation of complex unidentified mixtures of products.
It was shown that the primary amides of anthranilic acid reacted smoothly with 2 oxoglutaric acid. This transformation included easily accessible starting materials, and led to the formation of non-planar tricyclic compounds in high yields on multigram scale. Also, it was found that 2 oxoglutaric acid reacted with amides exclusively as 4-oxoacid.
Next, previously unreported partially saturated polycyclic quinazolin-4-one derivatives with a tertiary Carbon atom belonging to three cycles were obtained via the one-step reaction of anthranilic acid amides with cyclic oxoacid esters. This reaction proceeded diastereoselectively and provided the products with a relative cis-position of cycloalkane and butyrolactam cycles.
An approach towards the synthesis of partially saturated imidazo[1,2-a]quinazolones, e.g. 6,6a,8,9,10,10a-hexahydro-5H,11H-pyrrolo[1',2':3,4]imidazo[1,2-a]quinazoline-5,11-diones and 6,6a,10,10a-tetrahydro-5H,8H,11H-thiazolo[3',4':3,4]-imidazo[1,2-a]-quinazoline-5,11-diones with a different substituents at 6-position was disclosed. This transformation implemented the main idea of the simultaneous formation of pyrimidine and imidazole rings from the corresponding acyclic precursors with three nucleophilic centers (analogs of peptides based on anthranilic acid) and the synthetic equivalent of C 3+ (triethylorthoformate).
