Synthesis of thyroid hormone analogues. Part 2. Oxidative coupling approach to SK&F L-94901

A synthesis of L-3,5-dibromo-3′-[(6-oxo-l,6-dihydropyridazin-3-yl)methyl]thyronine-SK&F L-94901 (1), a novel, selective and potent thyromimetic – is described. The key step in this synthesis involves the formation of a hindered diaryl ether moiety. This paper describes an approach via oxidative coupling of the hindered phenols (2) and (3). Some by-products and impurities generated during the synthesis are discussed briefly.