Synthesis of regioisomeric 2,5‐bis‐substituted‐aza‐benzothiopyranoindazoles

The synthesis of 6‐chloro‐9‐nitro‐benzothiopyranopyridin‐5‐ones 2a, 2b and 2c has been accomplished. Chemotype 2d could not be prepared since attempts to cyclize 3‐(2‐nitro‐5‐chlorophenoxy)pyridine‐2‐carboxylic acid ( 1d ) led to the decarboxylation product 3‐(2‐nitro‐5‐chlorothiophenoxy) pyridine ( 40 ). Analogues 2a, 2b or 2c on treatment with the respectively substituted hydrazine led to the 2‐(substituted)‐5‐nitro 7, 8‐ or 9‐aza substituted chemotypes 3a‐7a, 8b , and 9c‐13c . The reduction of the nitro groups of these substrates was effected by treatment with hydrogen gas (palladium catalyst) or by stannous chloride to yield the 5‐amino chemotypes 15a‐18a, 20b and 21c‐24c , respectively. The conversion of these derivatives to the 2,5‐bis (alkylamino)‐7‐, 8‐ and 9‐aza benzothiopyranoindazoles listed in Table 3 was accomplished by direct alkylations, acylations, followed by reduction of the amido group with Red‐Al or lithium aluminum hydride, or by reductive alkylations in the presence of sodium cyanoborohydride. The removal of the protective BOC‐group was effected by treatment of the appropriate substrates with anhydrous hydrogen chloride to afford the respective hydrochloride salts listed in Table 4.