文摘
The development of a short and efficient synthesis of a complex 6-azaindole, BMS-663068, is described. Construction of the 6-azaindole core is quickly accomplished starting from a simple pyrrole, via a regioselective Friedel鈥揅rafts acylation, Pictet鈥揝pengler cyclization, and a radical-mediated aromatization. The synthesis leverages an unusual heterocyclic N-oxide 伪-bromination to functionalize a critical C鈥揌 bond, enabling a highly regioselective copper-mediated Ullmann鈥揋oldberg鈥揃uchwald coupling to install a challenging triazole substituent. This strategy resulted in an efficient 11 step linear synthesis of this complex clinical candidate.