Redirection of the Beckmann Rearrangement to Form Pyrrolidino[1,2- a ]benzimidazoles and Application to an Independent Synthetic Route to the Core of Balinatunfib

Abstract A proximal amine redirects the Beckmann rearrangement to a benzimidazole product. This transformation was repeated on the oxime of 1,2,3,4-Tetrahydro-5H-benzo[b]azepin-5-one where the product benzimidazole is additionally ortho-fused to pyrrolidine. This was exemplified by seven analogs, of which two, in independent parallel routes, were elaborated to (7R,14R/7S,14S)-6,7-Dihydro-7,14-methanobenzo[f]benzo[4,5]imidazo[1,2-a][1,4]diazocin-5(14H)-one, which is the core structure of competing tumor necrosis factor (TNF) inhibitor clinical candidates Balinatunfib and FT2109.