Fabio Fognini paid for a sloppy performance as he crashed out of the Internazionali d'Italia. Andrey Rublev and Milos Raonic also departed.
Lorenzo Musetti was three when Stan Wawrinka made his Internazionali d'Italia debut but the home hope downed the three-time grand slam king.
Andy Murray's US Open campaign ended with a second-round loss to Felix Auger-Aliassime.
Last year's US Open runner-up, Daniil Medvedev was in fine form in New York.
Novak Djokovic revelled in his triumphant display at the Western & Southern Open on Saturday.
Just two days before the US Open gets under way, Novak Djokovic showed why he is the favourite to win an 18th major title.
Milos Raonic awaits Novak Djokovic in the final in New York, with the world number one still yet to lose this season.
World number 30 Milos Raonic recognises the need to take stronger action and has challenged the tennis community to do more.
World number one Novak Djokovic was untroubled on his way to the Western & Southern Open semi-finals.
Top seed Novak Djokovic charged through on Tuesday, while Andy Murray lost to Milos Raonic in the last 16.