Abstract: The present disclosure provides pyrimidine compounds useful as tyrosine kinase inhibitors, and particularly epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) inhibitors. The disclosed EGFR inhibitors are effective against acquired resistance mutations appearing after treatment of existing EGFR inhibitors. The present disclosure also provides methods of treating cancer using pyrimidine compounds and pharmaceutical compositions comprising pyrimidine compounds. The methods of treating cancer may be directed to cancer with acquired resistance mutations.