A facile and highly convergent synthesis of biologically active spiro-fused thiadiazoline KSP inhibitors is reported. The highlights of the synthesis include the Michael reaction and cyclization of thiosemicarbazone to 1, 3, 4-thiadiazoline. This chemistry lends itself to the preparation of (+)-2, a potent and orally bioavailable anti-cancer agent, and to the development of a structure–activity relationship program.
