Selective amidation of 2,6-dihalogenopurines: application to the synthesis of new 2,6,9-trisubstituted purines.

We report herein the palladium(0)/Xantphos-catalyzed cross-coupling of various amides with 2,6-dihalogenopurines, with substituent-dependent regioselectivity. Furthermore, subjecting the same 2,6-dihalogenopurines to SNAr conditions with amide/NaH in DMF leads to inverted regioselectivity albeit in lower yield. These methodologies allow the two-step synthesis of new 2,6,9-trisubstituted purines from readily available 2,6-dihalogenopurines.