Synthesis of substituted thiazolo[4,5-b]pyridines and other annulated heterocycles via SN2→Thorpe–Ziegler→Thorpe–Guareschi domino reactions

A new combinatorial method for the preparation of substituted thiazolo[4,5-b]pyridines, which utilizes cyanoacetamide, heterocumulenes (isothiocyanates, carbon bisulfide), and ethyl-4-chloroacetoacetate in a new SN2→Thorpe–Ziegler→Thorpe–Guareschi domino reactions has been developed. The obtained thiazolo[4,5-b]pyridines were then used together with aldehydes and malononitrile in another Knoevenagel reaction→Michael reaction→hetero-Thorpe–Ziegler domino reaction for the synthesis of substituted 4,6-dihydro-5H-pyrano[2,3-d]thiazolo[4,5-b]pyridines.