I don’t know if this affects other versions of Photoshop, but on MacOS Photoshop CC 2017 frequently starts unexpectedly graying out all save buttons when you have made changes to your file and should be able to save.
The secret is to resize and move around the dialog. Drag the lower right corner to make it bigger and smaller a few times, and try dragging the whole dialog to the upper left corner of the screen and making it small.
This fixes it for me.