Preparation of the HIV Attachment Inhibitor BMS-663068. Part 7. Development of a Regioselective Ullmann–Goldberg–Buchwald Reaction

The discovery, development, and optimization of an Ullmann–Goldberg–Buchwald coupling reaction is described. This complex process represents a key transformation in the development of a commercially viable synthesis of the HIV attachment inhibitor prodrug BMS-663068. In this reaction, high regioselectivities were obtained for the coupling of a 1,2,4-triazole and a 7-bromoazaindole, preparing BMS-626529, the antepenultimate in good yield and quality. Key challenges associated with developing commercially viable conditions for this copper-mediated coupling include achieving the desired level of regiochemical control, identifying robust isolation conditions and controlling residual copper levels in the isolated product.