Efficient and regioselective N-1 alkylation of 4-chloropyrazolo[3,4-d]pyrimidine

Efficient and N-1 selective alkylation of 4-chloropyrazolo[3,4-d]pyrimidine can be achieved when the heterocycle is reacted with alcohols under Mitsunobu conditions. The 1-alkyl-pyrazolo[3,4-d]pyrimidines formed can be functionalized further according to known methods, to give a variety of 1,4-disubstituted pyrazolo[3,4-d]pyrimidines. The first example of a palladium-catalyzed coupling reaction on a 4-halopyrazolo[3,4-d]pyrimidine is described.