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Exchange 2013 send/receive problem with VPN

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Hello all.

We currentely have a problem with our Exchange 2013 server.
As first i'll explain the situation.

2 servers, both with Server 2012.
Server1: AD, DHCP, DNS, Exchange, RAS.
Server2: Filesharing, TS, SQL for our programs.
Both servers are running on Hyper-V.

The problem is simply, Exchange is running fine after a startup.
After a few hours receiving and sending emails it just stops.
When i disable the VPN everthing works fine, after enabling the VPN it will stop after a few hours.
There are some articles about the same problem, but haven't found any who has "solved" the problem after disabling the VPN.
With telnet we get the error: 451 4.7.0 Temporary server error. Please try again later. PRX5

We found the following log rules:

SmtpSend log:
2013-05-22T00:01:12.923Z,Inbound Proxy Internal Send Connector,08D021C110408447,0,,172.16.80.3:2525,*,,attempting to connect
2013-05-22T00:01:13.939Z,Inbound Proxy Internal Send Connector,08D021C110408447,1,,172.16.80.3:2525,*,,"Failed to connect. Error Code: 10061, Error Message: No connection could be made because the target machine actively refused it 172.16.80.3:2525"

SmtpReceive log:
2013-05-22T01:43:02.272Z,DC\Default Frontend DC,08D021C110408653,24,172.16.80.3:25,x.x.x.x:54917,*,,Proxy destination(s) obtained from OnProxyInboundMessage event
2013-05-22T01:43:02.272Z,DC\Default Frontend DC,08D021C110408653,25,172.16.80.3:25,x.x.x.x:54917,*,,"Message or connection acked with status Retry and response 451 4.4.0 Error encountered while communicating with primary target IP address: ""421 4.2.1 Unable to connect."" Attempted failover to alternate host, but that did not succeed. Either there are no alternate hosts, or delivery failed to all alternate hosts. The last endpoint attempted was 172.16.80.3:2525"
2013-05-22T01:43:02.303Z,DC\Default Frontend DC,08D021C110408653,26,172.16.80.3:25,x.x.x.x:54917,>,451 4.7.0 Temporary server error. Please try again later. PRX3 ,
2013-05-22T01:43:02.319Z,DC\Default Frontend DC,08D021C110408653,27,172.16.80.3:25,x.x.x.x:54917,<,RSET,
2013-05-22T01:43:02.319Z,DC\Default Frontend DC,08D021C110408653,28,172.16.80.3:25,x.x.x.x:54917,>,250 2.0.0 Resetting,
2013-05-22T01:43:02.319Z,DC\Default Frontend DC,08D021C110408653,29,172.16.80.3:25,x.x.x.x:54917,<,QUIT,
2013-05-22T01:43:02.319Z,DC\Default Frontend DC,08D021C110408653,30,172.16.80.3:25,x.x.x.x:54917,>,221 2.0.0 Service closing transmission channel,

Is there anyone who has an idea to solve this problem?

Thanks for your time!

Theun

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