The 36-year-old defeated Lopez 6-3, 6-3, 7-5 in a one-sided match.
Shapovalov defeated Jo-Wilfried Tsonga in straight sets in the second round of the 2017 US Open.
15-time Grand Slam champion faces Leonardo Mayer after lacklustre wins over Dusan Lajovic and Taro Daniel.
Nadal defeated Daniel in a 4-6, 6-3, 6-2, 6-2 victory.
Murray withdrew from the event right after the draw was made.
The Swiss ace also tried unconvincingly to explain to the kid why his fans call him the Goat.
Federer defeated Frances Tiafoe in a five-set victory on Tuesday (29 August).
The current World No. 1 was famously known for wearing capri-style shorts when he first entered the international tennis scene.
The former world number one defeated Halep 6-4, 4-6, 6-3.
Kota took the first set with relative ease but was overcome by the Serbian's fightback.
The top two-ranked players in the world could meet in the US Open semi-final.
Murray has not played any tennis after Wimbledon.
Kyrgios most recently reached the finals of the Cincinnati Masters.
Federer had to withdraw from the Cincinnati Open due to a back injury.
Three men can emerge from the final Grand Slam of 2017 at Flushing Meadows at the top of the ATP standings.
Swiss star could become the oldest world number one ever if he wins the latest Masters 1000 event.
Nadal is on course to regain his world number one ranking at the Rogers Cup.
The Swiss number two is "extremely disappointed" about not being able to defend title at Flushing Meadows.
Nadal will take the top spot if he reaches the semi-finals at the Rogers Cup.
Nadal could become the new world number one with a win in the Rogers Cup.
Federer will be looking for his sixth title of the year ahead of the US Open.
Thiem is one of many young players who are expected to be the new generation.