Polycondensed heterocycles. III. Synthesis of 5,11‐dioxo‐1,2,3,1 1a‐tetrahydro‐5H,11H‐ and 5‐oxo‐2,3,11,1 1a‐tetrahydro‐1H,5H‐pyrrolo[2,1‐c][1,4]benzothiazepine

Abstract The syntheses of 5,11‐dioxo‐1,2,3,11a‐tetrahydro‐5H11H‐ and 5‐oxo‐2,3,11,11a‐tetrahydro‐1H,5H‐pyrrolo‐[2,1‐c][1,4]benzothiazepine 10 and 11 have been studied. The former was obtained by intramolecular cyclization with CDI of N‐(2‐mercaptobenzoyl)‐L‐proline 19, prepared on one hand by demethylation of N‐(2‐methylthiobenzoyl)‐L‐proline t‐butyl ester 15, obtained via the Pummerer rearrangement of the corresponding sulphoxide 17 and successive alkaline hydrolysis, and by deprotection of the mercapto ester 18 with TFA or trimethylsilyl iodide. The ester 15 was achieved by reaction of o‐(methylthio)benzoic acid 12 with L‐proline t‐butyl ester or by treatment of the corresponding acid chloride 13 with L‐proline and successive esterification of N‐(2‐methylthiobenzoyl)‐L‐proline 16. On the other hand the proline 19 was also obtained by reduction with sodium dithionite of (S)‐bis[2‐[[2‐(hydroxycarbonyl)‐1‐pyrrolidinyl]carbonyl]phenyl] disulphide 20, prepared by condensation of bis(2‐chlorocarbonylphenyl) disulphide 14 with L‐proline. The reduction of (S)‐bis[2‐[[2‐(chloromethyl)‐1‐pyrrolidinyl]carbonyl]phenyl] disulphide 28 with sodium borohydride in boiling ethanol afforded directly the benzothiazepinone 11 in 85% yield. The disulphide 28 was synthesized treating the corresponding alcohol 24 or N‐(2‐mercaptoben‐zoyl)‐L‐prolinol 25 with thionyl chloride. Compound 25 was obtained by demethylation of the corresponding methylthio ether 26 oxidized to sulphoxide 27 via the Pummerer rearrangement. The acid chloride 14 by condensation with (S)‐2‐(chloromethyl)pyrrolidine hydrochloride gave disulphide 28 as well. The acid chlorides 13 and 14 by reaction with L‐prolinol provided respectively alcohols 26 and 24. Attempts to cyclodehydrate the mercapto alcohol 25, obtained also by reduction of disulphide 24, failed.