Tale of Two Protecting Groups—Boc vs SEM—for Directed Lithiation and C–C Bond Formation on a Pyrrolopyridazinone Core

Abstract

The importance of the “SEM” group, or the 2-(trimethylsilyl)ethoxymethyl group, as an N-protecting group for special class of pyrrolopyridazinones is reported. Our studies indicate that standard Boc protection on the nitrogen of a pyrrolopyridazinone results in significant decomposition during the incorporation of biaryl groups via Pd-catalyzed cross coupling reactions. However, on using the SEM group, the resulting cross coupling reaction gives excellent yields with no decomposition products, enabling the synthesis of a variety of compounds that were targeted for their antitumor activity.