You need to allow at least an hour at terminal from on-duty to depart and an hour from arrival to off-duty. On departure crews need time to review paperwork, have a job briefing, get on their train, have the dispatcher take them out of the yard. On arrival they need to pull into a low-speed yard track, put their power away, get to their off-duty point and complete any required paperwork. This can take longer sometimes too. So that means your crew has an absolute maximum of 10 hours on the road when planning crew change points.
Then it's a simple matter of distance and speed. Portland to Mechanicville is 267 miles. Average speed of 40mph is 6hrs, 40mins. Average speed of 30mph is just under 9 hours. And so on. So when you factor in train meets, passenger trains, and anything else that could delay you on the road you don't plan your crew run on maximum speed, it's some number less than that.
Portland to Ayer is 115 miles, plus another 28 or so to CP-45 in Worcester for a total of 143 miles. CP-45 to Selkirk is about 152. Portland to Keag is 200. So if you're running an overhead train Selkirk to Keag it's 495 miles. If you're planning an overhead train, Dover is probably a more realistic crew change point assuming equal average speeds on both sides. Keag is about 243 miles, Selkirk about 252 miles. You'd want to maintain an average speed of 30mph for a comfortable crew run - 8hrs on the road, 2hrs sign up/off, 2hrs buffer.
Trying to go Selkirk to Portland on one crew - about 295 miles - and assuming an average speed of 40mph is just under 7.5hrs. But there are places on the railroad that a mile long freight train will have to reduce speed and run under 40mph for several miles even if the mainlines are brought to 40mph. CP-45, Ayer Yard/Wye (even with a run-through track of some kind, it won't be 40), the Lowell Jct Wye, approaching/departing the terminal yards. In addition to meets, passenger trains or other delays, I wouldn't build this for more than a 30mph average speed, more realistically 25. 30mph gets you just under 10hrs while 25mph gets you just under 12. So it's doable, but also has to be well-timed with minimal delays on the trip