Synthesis of acyclic nucleotide analogues derived from 2-amino-6-C-substituted purines via cross-coupling reactions of 2-amino-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-6-halopurines with diverse organometallic reagents

Cross-coupling reactions of 2-amino-6-chloro-9-{2-[(diisopropoxyphosphoryl)methoxyl]-ethyl}purine (1) and 2-amino-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-6-iodopurine (2) with diverse types of organometallic reagents have been studied. Arylboronic acids reacted with 1 to give the corresponding 2-amino-6-arylpurines 3a-3d in good yields. Analogously, trialkylaluminium reagents were used for the preparation of 6-alkyl-2-aminopurines 3k and 31 from 1. Hetarylzinc halides and hetarylstannanes required the use of 2-amino-6-iodopurine 2 to give the corresponding 2-amino-6-hetarylpurines 3e-3j in fair to good yields. A CuI/KF mediated coupling of perfluoroalkylsilanes with 2 afforded the 2-amino-6-perfluoroalkylpurines 3m and 3n in moderate yields. Cleavage of the esters 3 with bromo(trimethyl)silane gave the target free phosphonates 4 that were purified by ion-exchange chromatography. The title compounds were tested on antiviral and cytostatic activity.