The A66 can be a 'mare as, like the A9, dualling is ad hoc and there are long chunks of single carriageway.
Friday might be OK southbound if you're off early.
There's a reasonable A road down the Welsh Marches which avoids the M5.
Personally I'd play it by ear making full use of G Maps and a radio station (Fiv Live?) to drive my route.
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