Yes, perfectly possible to do it in a day.

A train to London (either LNER to King’s Cross, or Avanti to Euston), Eurostar to Brussels, then ICE to Frankfurt Airport. Don’t worry about the 20 minute connection at Brussels, it’s normal.

Seat61 suggests the best place to make reservations - which for Eurostar is Rail Europe. I think that generally works from the US.

https://www.seat61.com/interrail-and-eurail-reservations.htm

Reservations on the UK train are optional. Reservations on the ICE are optional, except in summer - details for both on the above page.

No mandatory reservations on Brussels-Frankfurt anymore. That was only last year.

Currently in Europe travelled from Glasgow to Newcastle and got the ferry to Amsterdam. It worked out so much cheaper than paying eurostar reservstion fees.

Can you use that ferry for less than €35 (or €43)? That's a steal!

We paid £84 for 2 in a 2 bed

cabin overnight to Amsterdam arrived fresh and took the train to Hamburg 

Rail nerd question: Does this means they’ll run with two coupled neo’s on the busy moments in summer?

Don’t think so. See fernbahn.de or vagonweb.cz. In addition, HSL3 needs to be adapted to allow longer trains and that will only be ready by the end of next year.

​@Frankie If you could share how to get that Newcastle-Amsterdam bargain fare it would be brilliant? 

We booked the DFDS ferry I think through Direct Ferries. Just about everyone we met on the boat said what a great deal they got. One couple with one child paid around £130 return,  we only needed one way.

Yeah I also saw that deal (but didn't book) for multiple dates in January-February. Those prices are just not gonna happen in summer though. ;)