Regioselective preparation of N-7- and N-9-alkyl derivatives of N-6-[(dimethylamino)methylene]adenine bearing an active methylene group and their further derivatization leading to alpha-branched acyclic nucleoside analogues

N-7- and N-9-regioisomers of cyanomethyl and trifluoroethyl-N-6-[(dimethyla mino)methylene]adenine (1, 2, 6, 7) were prepared regioselectively, the for mer by the direct alkylation of N-6-[(dimethylamino)methylene]adenine, the latter by the alkylation of adenine followed by protection of the amino gro up. These derivatives, which bear an active methylene group, were submitted to reactions with allyl bromide, aldehydes or tert-butoxybis(dimethylamino )methane in order to modify their side chain. In this way, several new alph a-branched acyclic adenosine analogues (8, 10-16) were prepared; the regios electivity of the alkylation and the product structures were determined by H-1- and C-13-NMR spectroscopy. N-15-NMR parameters for selected compounds were studied by gradient-enhanced inverse-detected techniques. In addition, X-ray data of derivatives 1, 2 and 7 are reported.