Sounds like your main jet/circuit is the problem.
The main jet circuit comes into play at around 75-100% throttle, which overlaps somewhat with the needle circuit.

It's hard to tune in low gears because the engine just muscles right past the bad spots due to insufficient loads.
If the engine isn't being loaded up like a high gear would, it can still have more than adequate power to accelerate under lightly loaded conditions.
The rough spots in tuning hardly even feel like hesitations, and before you realize something isn't tuned right it's already time to shift to another gear.
That's the purpose of putting it into high gear, because it takes the engine much longer to increase RPM due to high load conditions and even slightly out of tune circuits will be magnified.
If your main jet is the culprit, it'll feel like you're hitting a rev limiter at a certain point on the thumb throttle's travel, like at 75% or 85% throttle travel, for example.
If it's a fuel flow issue, it might scream in 6th for a few seconds before it starts falling on its face.
It might feel great at full throttle for a few seconds but once you empty the carb's bowl you might not be able to get it past 50% throttle until you let off the throttle long enough for the fuel to catch up again.
A minor fuel flow issue may require several runs or a long time at full throttle to drain the bowl and cause issues, and may flow fast enough that you wouldn't have to let it sit at low throttle position for it to catch up.
Fuel flow issues have varying degrees of severity, but main jet issues always occur at certain throttle positions.

Try cleaning the carb first, then tune the main jet.
It's not hard to completely clean the carb, just lay it out like you would when disassembling a gun and take a few pics just in case.
Use a can of carb cleaner and squirt it all the way through every passage ensuring that it comes out the other end (also a great way to learn what all the passages and such do in the carb!)
Reassemble and see if your problem is fixed, if not, then start changing out main jets.
Start off by going richer, one jet at a time (main jets get richer as the numbers get bigger).
You're probably 2 jets off...that's how it normally works, if it's running rough enough that you think it's a problem then you're several sizes off.
Not as easy to tell the difference in just one jet size.
If going richer is making it worse, go a size smaller than your original jet size and see if it gets better.
Be sure to buy plenty of jets, both larger and smaller, so you don't have to worry about running out of richer or leaner jets to try.
While you're at it, go ahead and buy pilot jets and a few needles since you'll probably be putting in an order online for them.
You do need to re-tune for summer and winter temps, there is no "one jet fits all" for year round riding, and there's no specific jetting that works for all 250's (not even baseline jetting, really).
Use your existing jetting as a baseline and work from there, write everything you've done in a little notepad to keep track of what all jets you've tried, how many turns on the pilot air screw, needle clip position, outside air temperature when you were tuning, etc.

Ok, a few things you should know about jetting.
-Learn about plug chops, they're vital to understanding your engine's state of tune.
-Learn about air leaks and how they affect your tuning (you can easily melt a piston with nothing more than a small air leak) and how a leak down tester works.
-It's best to start with the idle circuit, then needle, then work up to the main...but since you're only having trouble with the main it's probably not necessary.
-Tune your engine after all other factors have been addressed that might affect tuning (air leaks, air filter, fuel flow, fuel filter, float level, bad fuel, worn out reeds, low compression from high time rings, leaking head gasket, incorrect spark plug, etc.)

Basically, anything that might affect tuning should be fixed first, because tuning in itself is demanding enough.

As far as your fuel filter goes, replace it or simply remove it.
So long as your fuel is clean and your tank is clean, you don't need it.
I've run a 250 for 200+hrs without a filter and never had a problem with trash getting into the carb.
ChrisG sold me a few tank condoms, which basically pre-filters the fuel as you're pouring it in...so if you had one of those and your tank was clean a fuel filter would be completely unnecessary.
Not sure if he's still selling them, but they were pretty reasonably priced and you could wash contaminants and trash off whenever they caught anything.

For now, just remove the fuel filter and run a line straight to the carb, drain the tank and replace with fresh fuel, clean the carb, and see what happens.
You might even try a few gallons of 100LL just to be sure you're not detonating too, find it at the local airport.