The invention provides a chemical entity of Formula (I): (I), wherein R1, R2, R3, and R4, have any of the values described herein, and compositions comprising such chemical entities methods of making them and their use in a wide range of methods, including metabolic and reaction kinetic studies detection and imaging techniques radioactive treatments modulating and treating disorders mediated by PDE2 activity treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma- dependent losses of function treating stroke, including cognitive and motor deficits during stroke rehabilitation facilitating neuroprotection and neurorecovery enhancing the efficiency of cognitive and motor training and treating peripheral disorders, including hematological, cardiovascular, gastroenterological, and dermatological disorders.