Scalable and Straightforward Synthesis of a 2-Alkyl-7-Arylbenzo­thiophene as a GPR52 Agonist via a Hemithioindigo Derivative

Abstract

A simple and efficient procedure has been developed for the synthesis of the GPR52 agonist N-(2-amino-2-oxoethyl)-3-{4-fluoro-2-[3-(trifluoromethyl)benzyl]-1-benzothien-7-yl}benzamide. The benzothiophene unit was directly constructed by reduction of a hemithioindigo derivative prepared by an intramolecular Friedel-Crafts cyclization of (phenylsulfanyl)acetic acid, followed by dehydrative benzylidene formation.

Iodine-Containing 4,7-Dihalobenzo[b]thiophene Building Blocks and Related Iodobenzo[b]thiophenes: Promising Molecular Scaffolds for Bio-Inspired Molecular Architecture

“…Preparation of the precursors of this category may be easier than other methods. [90][91][92][93][94][95][96] However, regioselectivity become a problem in specific cases. For example, products 64 and 65 in Scheme 29 were not separated through column chromatographic treatment.…”

“…For example, products 64 and 65 in Scheme 29 were not separated through column chromatographic treatment. 95 In Scheme 30, structurally similar ketone 66 92 and ester 67 93 were prepared from different sulfur compounds and converted into 3-and 2-substituted benzo[b]thiophenes, respectively. Reaction of thiophenol with substituted propiolates in the presence of iodine and di-t-butyl peroxide (DTBP) led to benzo[b]thiophenes (Scheme 30).…”

Et3N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

“…Specifically, thioaurones and their analogs show a variety of biological activities such as anticancer [24], inhibition of tyrosine phosphatase 1B, antioxidant properties, etc. [25][26][27]. Due to their numerous applications, they have found diverse uses such as thioindigo-like dyes, photoresponsive devices, and photoswitchable biomolecules [28][29][30][31].…”