Abstract: | The drug candidates ( 2 ) and ( 3 ) are highly potent LFA‐1 inhibitors. They were efficiently prepared labeled with carbon‐14 using a palladium‐catalyzed carboxylation of an iodo‐precursor ( 5 ) and sodium formate‐14C to afford acid 14C]‐( 6 ), which was coupled via an amide bond to chiral amines ( 7 ) and ( 8 ) in 52% and 48% overall yield, respectively, and with specific activities higher than 56 mCi/mmol and radiochemical purities of 99%. For stable isotopes synthesis, the amine 2H8]‐( 7 ) was synthesized in three steps from 2‐cyanopyridine‐2H4 using Kulinkovich‐Szymonik aminocyclopropanation, followed by coupling to L ‐alanine‐2,3,3,3‐2H4‐N‐t‐BOC, and then removal of the BOC‐protecting group. Amide bond formation with acid ( 6 ) gave 2H8]‐( 2 ) in 36% overall yield. The amine 13C4,15N]‐( 8 ) was obtained in two steps using L‐threonine‐14C4,15N and then coupled to acid 13C]‐( 6 ) to give 13C5,15N]‐( 3 ) in 56% overall yield. |