Microsoft have announced that .Net 4.5, 4.6 and 4.6.1 are going to be end of life by April 26, 2022.
So as per my blog BizTalk supported Microsoft .Net Frameworks that is going to mean that BizTalk 2013 which can only run on .Net 4.5 that will no longer be getting patches. So if you haven’t been thinking about upgrading BizTalk, now is probably time to start thinking about that.
BizTalk 2013 R2 can run on .Net is 4.6, so make sure you have installed .Net 4.6.2
If you are running BizTalk 2016 with .Net 4.6 you will want to make sure you are at 4.6.2 or either go to .Net 4.7.2 (with at least CU2), or .Net 4.8 (with CU7 and above).
BizTalk 2020 will be running on 4.7.2, but I’m sure Microsoft will support .Net 4.8 for that soon as well.