Synthesis, Characterization and In Vitro Antibacterial Evaluation of Novel 4-(1-(Pyrimidin-4-yl)Ethyl)-12H-Pyrimido[4′,5′:5,6][1,4]Thiazino[2,3-b]Quinoxaline Derivatives

A new methodology for the synthesis of 4-(1-(pyrimidin-4-yl)ethyl)-12H-pyrimido[4 ',5 ':5,6][1,4]thiazino[2,3-b]quinoxaline derivatives 5a-g was introduced. Condensation of 5-bromo-4-[1-(5-bromo-2,6-dichloropyrimidin-4-yl)ethyl]-2-chloro-6-methylpyrimidine 2 and 3-aminoquinoxaline-2-thiol 3 gave either regioisomers 4 or 4 '. The computational and spectral data of both regioisomers confirmed the occurrence of the S/N type Smiles rearrangement during the course of the reaction. Treatment of the foregoing compound with various secondary amines gave several new 4-(1-(pyrimidin-4-yl)ethyl)-12H-pyrimido[4 ',5 ':5,6][1,4]thiazino[2,3-b]quinoxaline derivatives 5a-g. The newly synthesized compounds were evaluated for their potential antibacterial activity and the results exhibit two of the derivatives are moderately valuable compounds in comparison with three reference drugs.

Automated summary

A new methodology for synthesizing pyrimido[4 ',5':5,6][1,4]thiazino[2,3-b]quinoxaline derivatives was introduced, with the occurrence of S/N type Smiles rearrangement confirmed during the reaction. The newly synthesized compounds were evaluated for potential antibacterial activity, with two showing moderate value compared to three reference drugs.