The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades. Certain disclosed embodiments concern contacting compounds having a formula or a salt or N-oxide thereof, with 2,4-dichloro-5-fluoropyrimidine under conditions to provide compounds having a formula