<script type="text/javascript">
var prm = Sys.WebForms.PageRequestManager.getInstance();
prm.add_initializeRequest(InitializeRequest);
prm.add_endRequest(EndRequest);

function InitializeRequest(sender, args) {
   document.getElementById("ButtonToDisable").disabled = true;
}

function EndRequest(sender, args) {
   document.getElementById("ButtonToDisable").disabled = false;
}
</script>

Sys.WebForms.PageRequestManager.getInstance().add_initializeRequest(CheckStatus);
function CheckStatus(sender, arg)
{
   var postBackElement = arg.get_postBackElement();
   var prm = Sys.WebForms.PageRequestManager.getInstance();
   if (prm.get_isInAsyncPostBack() && postBackElement.id == "btn1") {
      arg.set_cancel(true);
      //display friendly message, etc
   }
}