Preparation of the pyridylpiperazine moiety starts by aromatic displacement of chlorine from 2-chloro-3-nitropyridine by piperazine to give 3. The secondary amine is then protected as its BOC derivative by reaction with
catalytic hydrogenation. Reductive alkylation with acetaldehyde in the presence of lithium cyanoborohydride gives the corresponding N-ethyl derivative. The protecting group is then removed by reaction with TFA
. Reaction of the resulting amine with the imidazolide derivative of 5-methoxy-3-indoleacetic acid produces the amide reverse transcriptase inhibitor, atevirdine.
^WO 9109849, Romero, Donna Lee; Mitchell, Mark Allen & Thomas, Richard Charles et al., "Diaromatic substituted anti-AIDS compounds", published 1991-07-11, assigned to Upjohn
