On the Options #2 screen, Advanced Options, COMs section, be sure COM1 is selected if that is what you are using, as the Auto setting does not work with all third-party aircraft. If the problem persists, please zip the debug_monitor.log file from your PF3\Logs folder and attach it to your reply post. It will help us see what is happening with the settings. The file must be zipped to be attached. (If the problem flight is not your most recent flight, zip and attach your whole PF3\Logs folder and hopefully the log will still be there.)
As Dan says, use Com 1 or Com 2 as your default.
I use PMDG 747 for both FS2004 & FSX and it works just fine,