The reaction of 2,4-halopyrimidines with nucleophiles generally leads to selective displacement of the halide at the 4-position:1
In their textbook, Joule and Mills don't explain why, though, simply saying that it "is the normal situation for nucleophilic – 4-chloro > 2-chloro".
I don't see any obvious difference in the stability of the anionic intermediates, either (the so-called Meisenheimer complexes).
What can explain the regioselectivity of the above reaction?
- Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley: Chichester, U.K., 2010, p 257.