A simple facile synthesis of substituted purine derivativeshas been developed by using Mitsunobu conditions for analcohol and a respective nucleobase. A wide range ofalcohols produces good to excellent yield (>90%). Theresulting purine analogues show good regioselectivity withN-9 substitution as the dominant products in most of thecases. Application of diastereospecific alcohols reveals acomplete inversion of the carbon stereogenic center givinga single diastereomer. More than two dozen novel nucleobasederivatives have been prepared in high yield.