PYRAZOLO[4,3-D]PYRIMIDINES - REGIOSELECTIVITY OF N-ALKYLATION - FORMATION, REARRANGEMENT, AND ALDEHYDE COUPLING REACTIONS OF 3-LITHIO DERIVATIVES

N-Alkylation reactions of 3-bromopyrazolo[4, 3-d]pyrimidin-7-one and 3-bromo-7-chloro- and 3-bromo-7-methoxypyrazolo[4, 3-d]pyrimidines were studied. Alkylations in aqueous base yielded predominately N-l alkyl products, as did trimethysilylation using hexamethyldisilazane. In contrast, alkylation with 2-chlorotetrahydropyran and sodium hydride in dimethylformamide or with dihydropyran and an acid catalyst in ethyl acetate yielded predominantly N-2 alkyl products. Formation of 3-lithio derivatives of N-l and N-2 alkylated 7-alkoxypyrazolo[4, 3-d]pyrimidines from the corresponding 3-bromo compounds was accomplished by treatment with n-butyllithium at low temperatures. N-l alkyl compounds yield complex mixtures of products, including those of N-dealkylation and rearrangement with rupture of the pyrazole ring. The N-2 alkylated compound, 3-lithio-7-methoxy-2-tetrahydropyran-2'-ylpyrazolo[4, 3-d]pyrimidine, was stable and reacted with benzaldehyde in high yield. © 1979, American Chemical Society. All rights reserved.