The regioselective amination of substituted di- and trichloropyrimidines affording the 2-substituted products is reported. While aryl- and heteroarylamines require the use of a dialkylbiarylphosphine-derived palladium catalyst for high efficiency, more nucleophilic dialkylamines produce 2-aminopyrimidines under noncatalyzed SNAr conditions. The key is the use of 5-trimethylsilyl-2,4-dichloropyrimidine as a surrogate for the parent dichloropyrimidine. For more challenging cases, the 2-chloro-4-thiomethoxy analogues were prepared and exclusively afford the desired 2-aminated-4-thiomethoxypyrimidine products.The regioselective amination of substituted di- and trichloropyrimidines affording the 2-substituted products is reported. While aryl- and heteroarylamines require the use of a dialkylbiarylphosphine-derived palladium catalyst for high efficiency, more nucleophilic dialkylamines produce 2-aminopyrimidines under noncatalyzed SNAr conditions. The key is the use of 5-trimethylsilyl-2,4-dichloropyrimidine as a surrogate for the parent dichloropyrimidine. For more challenging cases, the 2-chloro-4-thiomethoxy analogues were prepared and exclusively afford the desired 2-aminated-4-thiomethoxypyrimidine products.