There are a few things needed to troubleshoot these kinds of errors, though knowing how they're generated is the first step. This error is a very, very standard error for SMTP mailers of all types; it's the delivery delay notice given when the first few attempts to send mail to a mailer fail (generally for connectivity reasons, though others like 'mailbox full' can also cause this). If a mail is rejected for a specific reason, such as an SMTP-550-Not-Allowed error that generates a different message. But for "the destination mailer isn't talking", this is the message that gets generated.
Knowing that, you can take the message that generated the delay message and look at the To: line. That will tell you what mailer your Exchange system can't contact.
If the To: is an internal user, you have a problem inside Exchange. I'm not sure if SBS has it, but hunt up the Message Tracking tool and try to see how that message got routed.
If the To: is an external user, but not all external mail fails, then you need to investigate why your Exchange server can't talk to that domain. The techniques for this vary, depending on the exact failure. Again, I'm not sure if SBS has this option but you can turn on 'protocol level logging' which will provide detailed logs for every SMTP transaction (this gets very, very spammy); clues may hide within.
If the To: is an external user, and all external mail fails this way, then you need to look into your Exchange external-connector settings since that's probably where the problem is.