Synthesis, Reactions, and Antimicrobial Activity of Novel Heterocyclic Compounds Containing Cyclopenta[d]thieno[2,3-b]pyridine Moiety and Related Fused Heterocycles

Abstract

We describe a simple method to synthesize novel 4-cyano-1-morpholin-4-yl-6,7-dihydro-5H-cyclopenta[c]pyridine-3-thione by the reaction of 3-amino-1-thioxo-1,5,6,7-tetrahydrocyclopenta[c]thiopyran-4-carbonitrile with morpholine through Dimroth rearrangement. The 1-amino-5-morpholin-4-yl-7,8-dihydro-6H-cyclopenta[d]thieno[2,3-b]pyridine-2-carboxamide, which was synthesized by two methods, was used as a versatile precursor for synthesis of new thienopyrimidines fused to cyclopenta[d]pyridine ring system. Consequently, reaction of the amino-carboxamide with diethylmalonate, triethyl orthoformate, and cycloalkanones afforded the corresponding fused pyrimidine heterocycles. On the other hand, chloroacetylation of the amino-carboxamide using chloroacetyl chloride in dioxane produced the chloroacetyl amino derivative that in turn underwent cyclocondensation upon reaction with acetic anhydride to give the chloromethyl pyrimidinone. The latter compound was subjected to react with various nitrogen nucleophiles by nucleophilic substitution reactions to yield the akyl (aryl)amino methyl pyrimidinones. Subsequently, treatment of the phenyl aminomethyl derivative with formaldehyde under Mannich conditions produced the imidazopyridothienopyrimidine ring system. Similarly, reaction of the phenyl aminomethyl pyrimidonone with chloroacetyl chloride afforded a new heterocyclic system namely, cyclopentapyridothienopyrimidopyrazine. On the other hand, reaction of the amino-carboxamide with carbon disulfide in pyridine led to the formation of oxopyrimidine thione, which was alkylated by the reaction with different α-halo carbonyl compounds. The newly synthesized compounds were fully characterized on the basis of elemental and spectral analyses. Alternatively, some of these compounds revealed promising antibacterial and antifungal activities through the in vitro screening.