Just sharing my recent experience:
Upgrade from 20.115.0039 to 21.100.0127 failed with the following error message:
Upgrade process has been interrupted. The database cannot be upgraded because your current build 20.115.0039 is incompatible with the build 21.100.0127. Wait for the next update package that will be compatible with your current build.
Note: Release Notes indicate that migrating from 2020R1 is direct.
I was glad to find out that upgrading instance in build 20.206.0011 to 21.100.0127 was successful (including Portal).