Heterocycles with a benzothiadiazepine moiety. 3. Synthesis of imidazo[5,1‐ d ]pyrrolo[1,2‐ b ][1,2,5]benzothiadiazepine 9,9‐dioxide

The synthesis of imidazo[5,1‐ d ]pyrrolo[1,2‐ b ][1,2,5]benzothiadiazepine 9,9‐dioxide ( 5 ), a novel sulfur‐containing tetracyclic benzodiazepine, is reported starting from pyrrolo[1,2‐ b ][1,2,5]benzothiadiazepine 5,5‐diox‐ide ( 6 ) by cycloaddition of tosylmethyl isocyanide to the azomethine double bond. Pyrrolobenzothiadiazepine 6 was obtained by iron powder/acetic acid reduction of 1‐(2‐nitrobenzenefulfonyl)pyrrole‐2‐carboxaldehyde ( 7 ) and subsequent ring closure of intermediate aminoaldehyde or by cyclization of 1‐(2‐formamidobenzene‐sulfonyl)pyrrole ( 8 ) with phosphorus oxychloride via a Bischler‐Napieralski reaction. Formylation of 1‐(2‐ami‐nobenzenesulfonyl)pyrrole with acetic‐formic anhydride gave 8. The structure of 5 was confirmed by oxidation with activated manganese dioxide of dihydro derivative 9 , obtained through cyclization of 11‐amino‐methyl‐10,11‐dihydropyrrolo[1,2‐ b ][1,2,5]benzothiadiazepine 5,5‐dioxide ( 10 ) with triethyl orthoformate. The last compound was prepared alternatively by catalytic reduction of nitro derivative 11 , obtained by addition of nitromethane to pyrrolobenzothiadiazepine 6 , or by lithium aluminum hydride/sulfuric acid reduction of amide 13 , synthesized starting from ethyl 10,11‐dihydropyrrolo[1,2‐ b ][1,2,5]benzothiadiazepine‐11‐carboxyl‐ate 5,5‐dioxide.