Nonracemic Synthesis of GK–GKRP Disruptor AMG-3969

A nonracemic synthesis of the glucokinase–glucokinase regulatory protein disruptor AMG-3969 (5) 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.