The design of some novel disubstituted 7,8-dihydro-6H-5,8-ethanopyrido[3,2-d]pyrimidine derivatives is reported. The series was developed from quinuclidinone, which afforded versatile platforms bearing one lactam function in position C-2 that were then used to create C–N or C–C bonds for S_NAr or palladium-catalyzed cross-coupling reactions by in situ C–O activation. The reaction conditions were optimized under microwave irradiation, and a wide range of amines or boronic acids were used to determine the scope and limitations of each method. To complete this study, the X-ray crystallographic data of 7,8-dihydro-6H-5,8-ethanopyrido[3,2-d]pyrimidine derivative 49 were used to formally establish the structures of the products.