Nonracemic Synthesis of GK–GKRP Disruptor AMG-3969

A nonracemic synthesis of the glucokinase– glucokinase regulatory proteindisruptor AMG-3969 (5) is reported. Key features of the synthetic approach are an asymmetric synthesis of the 2- alkynyl piperazinecore via a base-promoted isomerization and a revised approach to the synthesis of the aminopyridinesulfonamide with an improved safety profile.