I've been considering this as well, but I haven't actually progressed beyond mocking up the engine into a CB500 frame. You can slide the 650 into a 500 frame by removing the sump and the tensioner, although I didn't do the tensioner because I had a bare frame I could lift around it.
The 650 carbs, whether they're mech slides or CV, have a shorter intake passage and sit closer to the head, therefore farther away from the airbox. Plenty of room to get the airbox in there, but it doesn't fit the frame perfectly, and the filter is on the extension and it goes where the battery is on a 500. You'd have to make something work. It helps if you have a complete parts bike to look at.
I should think that there wouldn't be any big showstoppers, just a few little ones, but then, I stopped on this project, temporarily at least.