Development of a Practical Synthesis of Stearoyl-CoA Desaturase (SCD1) Inhibitor MK-8245

A practical kilogram scale chromatography-free synthesis of stearoyl-CoA desaturase 1 (SCD1) inhibitor MK-8245 is described. The key features of this sequence include an efficient addition elimination reaction of a piperidine fragment with a 3-bromoisoxaline followed by an iodine-mediated oxidation to the corresponding isoxazole. The development of a safe and scalable tetrazole formation protocol is also presented.