Ole Gunnar Solskjaer looks set to sign his first player of the summer in the shape of Donny van de Beek.
A £34m offer plus £4m in add-ons was accepted from Ajax but United have two more players in their sights.
A creative midfielder was a priority but a right-winger and a centre-back is also high on the wishlist.
Jadon Sancho remains the top target for the former but Solskjaer was keen on bolstering his defence next.
Upamecano had been identified as the man to do just that, but RB Leipzig are not interested in a bid.
According to transfer guru Fabrizio Romano, the German club do not need to sell anymore players this summer.
And that is because of Chelsea, who acquired Werner earlier in the transfer window after they met his release clause of £50m.
The Blues have been splashing the cash this summer, with Werner one of several arrivals at Stamford Bridge.
As well as the Germany international, Hakim Ziyech, Thiago Silva, Ben Chilwell and Malang Sarr have all joined.
But the signing of Werner looks set to have a knock-on effect with Leipzig now confident of keeping hold of Upamecano.
The Frenchman has had a fine campaign in the Bundesliga and has become one of the most sought-after players in Europe.
His performances helped the German outfit reach the semi-finals of the Champions League, the furthest they have got in the competition.
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And the 21-year-old has admitted talks have been held over a prospective transfer in the remaining weeks of the window.
"I extended in Leipzig, because I feel good with my team-mates and my coach. I’m good at Leipzig," said Upamecano.
"It’s true that I’m in great demand. I speak with clubs, but I’m in no rush and we’ll see what happens in the future."