A mild and selective C6 arylation strategy for pyrrolo[2,3-d]pyrimidine derivatives with arylboronic acids at room temperature is described. This unified protocol has been achieved by the synergistic combination of Pd(II)/TEMPO catalysis and CF3CO2H promotion under silver-, base-, and additive-free conditions. The broad substrate scope, good functional group tolerance, excellent regioselectivity, and air and moisture tolerant conditions make this process attractive for the effective synthesis and modification of targeted small molecule drugs.