Scalable Synthesis of a Dual TLR7/8 Agonist via Highly Selective <i>N</i> 2-Alkylation of 1 <i>H</i> -Pyrazolo[4,3- <i>d</i> ]pyrimidine

We report a scalable synthesis of a potent dual TLR7/8 agonist featuring a pyrazolopyrimidine core. An acid-mediated selective <i>N</i>2-alkylation of 1<i>H</i>-pyrazolo[4,3-<i>d</i>]pyrimidine with free benzyl alcohol furnishes the <i>N</i>2-alkylated product in 72% yield with high regioselectivity (14:1 <i>N</i>2/<i>N</i>1). Subsequent copper-catalyzed amination with aqueous ammonia installs the <i>C</i>5 amino group in 70% yield, avoiding azides or complex ammonia surrogates. The convergent sequence proceeds in 34% overall yield from readily available materials and is amenable to kilogram-scale production.