Scheme 15.

Synthetic scheme for generating ebselen (73). Reagents and Conditions: (i) (1) DCM, pyridine, SOCl₂, reflux, 2 h; (2) toluene, aniline, reflux, 3 h, 80%; (ii) dry THF, n-BuLi, nitrogen atmosphere, 0 °C, 30 min, 76% (determined via methylation of 72); (iii) same solution as step (ii), Se, 0 °C, 30 min; (iv) same solution as step (iii), CuBr₂, 30 min at −78 °C, then 2 h at RT, 63%. Adapted with permission from [147], copyright 1989 American Chemical Society, and [148], copyright 2003 The Pharmaceutical Society of Japan.