Trenzalore was a place that, according to Dorium Maldovar, the Doctor would visit at some point in his travels (at the fall of the eleventh). Here, the First Question in the universe would be asked and "no living thing could speak falsely or fail to answer."
The Silence were determined that for whatever reason, the question's answer would never be revealed. Their plan was that the Doctor should never reach Trenzalore because (a better translation of their core belief is that) "silence must fall when the question is asked." (DW: The Wedding of River Song)