An expedient synthesis of face ‘b’ pyrido-annulated analogs of 1,5-benzothiazepines of medicinal interest

Abstract

An expedient protocol for the synthesis of face 'b' pyrido-annulated analogs of 1,5-benzothiazepines, namely 4-(methylthio)-5-(1 ,3 ,4 -oxadiazol-2 -yl)-2-phenyl-5,11-dihydrobenzo[b] pyrido[2,3-e] [1,5] thiazepine-S,S-dioxides 9a-9f, of medicinal interest emerged to exploit the potential of 3-ketene dithioacetal-substituted derivatives of 4-(1 ,3 ,4 -oxadiazol-2 -yl)-2,3-dihydrobenzo[b] [1,5] thiazepin-2(1H)-one-S,S-dioxide 8. This latter compound 8 was obtained from the base-catalyzed condensation of CS 2 and MeI with 4-(1 ,3 ,4 -oxadiazol-2 -yl)-2,3-dihydrobenzo[b] [1,5] thiazepin-2(1H)-one-S,S-dioxide (7). Compound 7 was available from ethyl-2-oxo-2,3,4,5-tetrahydro-[1,5]-benzothiazepin-4-carboxylate (3) on applying established synthetic procedures, which had been previously employed in the literature on related substrates. Treatment of 8 with the anions derived from substituted acetophenones formed the diones which underwent facile cyclocondensation with NH 4 OAc in AcOH to yield the desired products 9a-9f in acceptable yields.