Synthesis and evaluation of variably substituted N-methyl tetrahydroisoquinolines and benzazepines as monoamine reuptake inhibitors

Transition‐Metal‐Free Methods for the Remote C−H Bond Functionalization of Cyclic Amines

“…Notably, it was found earlier by the same group that s ‐BuLi deprotonates C−H bond at 1‐position in the presence of equimolar amount of BF 3 ⋅OEt 2 , due to the reversed electronic property of the amine nitrogen upon coordination to BF 3 [51] . Lata and co‐workers later modified this reaction using ketones as electrophiles instead of benzynes, and synthesized a variety of N ‐methyl‐THIQ and benzazepine derivatives featuring a tertiary alcohol substituent at the remote benzylic position [52] . Due to the resemblance in structure of these compounds to Venlafaxin, an antidepressant, their activities as monoamine reuptake inhibitor are also evaluated.…”

“…[51] Lata and co-workers later modified this reaction using ketones as electrophiles instead of benzynes, and synthesized a variety of N-methyl-THIQ and benzazepine derivatives featuring a tertiary alcohol substituent at the remote benzylic position. [52] Due to the resemblance in structure of these compounds to Venlafaxin, an antidepressant, their activities as monoamine reuptake inhibitor are also evaluated. In 2019, Kovács and coworkers reported the formation of tetrahydro-2,5methanobenzo[c]azepines such as compound 57 via β-lithiation of THIQs followed by nucleophilic addition of the generated carbanion to the N-tethered epoxyethane moiety (Scheme 23).…”