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-dioxide (6) by cycloaddition of tosylmethyl isocyanide to the azomethine double bond. Pyrrolobenzothiadiazepine 6 was obtained by iron powder/acetic acid reduction of 142-nitrobenzenesulfonyl)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-aminobenzenesulfonyl)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-aminomethyl-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-carboxylate 5,5-dioxide.