Synthesis of Some Thiophene-fused Azepino[5,4,3-cd]indoles

Abstract

Interaction of indolylzinc chloride with 2-chloro-3-nitrothiophene gave 3-(3- nitrothien-2-yl)indole ( 7) which was converted, via reduction followed by acylation, into 3-(3-acylaminothien-2-yl)indoles (9a-c).Cyclization of 9a-c induced by phosphorus oxychloride under Bischler-Napieralski reaction conditions, took place regioselectively at the indolic C-4 locus to furnish the respective thieno[2',3' : 6,7]azepino [5,4,3-cd]indoles (3a-c).On the other hand, the azepino[5,4,3-cd]indole system constitutes the skeleton of the ergot alkaloid claviciptic acid (2). 11Some synthetic analogs of 2 were reported to exhibit potent activity on the central nervous system with potential against migraine attacks, 12 while others were described as dopamine D-1 receptor ligands, 13 useful for treatment of circulatory and digestive tract disorders, 14 as psychotropics, 14 diuretics and smooth muscle relaxants.