Nonracemic Synthesis of GK–GKRP Disruptor AMG-3969

A nonracemic synthesis of the gluco­kinase–gluco­kinase regulatory protein disruptor AMG-3969 (<b>5</b>) is reported. Key features of the synthetic approach are an asymmetric synthesis of the 2-alkynyl piperazine core via a base-promoted isomerization and a revised approach to the synthesis of the amino­pyridine­sulfona­mide with an improved safety profile.