The draw for the Copa Libertadores round of 16 took place in Paraguay on Monday.
Wednesday's results left all three teams on 10 points but Flamengo (+6) and LDU Quito (+4) pipped Penarol (+2) on goal difference.
Palmeiras reached the knockout phase thanks to a 4-0 rout of Melgar, while San Lorenzo also progressed despite their 1-0 loss to Junior.
Boca Juniors scored four goals against Jorge Wilstermann on Wednesday, after Cruzeiro's Fred celebrated a first-half hat-trick.
Marco Ruben led Athletico Paranaense to an impressive win over Boca Juniors in the Copa Libertadores.
Boca Juniors and Palmeiras both won 3-0 in the Copa Libertadores on Tuesday.
Defending champions River Plate snatched a last-gasp draw at Alianza Lima on Wednesday.
We assess the leading candidates for glory and the potential stars ahead of the start of the 2019 Copa Libertadores.
With two years left on a lucrative contract at Shanghai SIPG, Hulk does not anticipate moving to Palmeiras for the 2019 season.
Boca assistant Gustavo Barros Schelotto is expecting a tough battle in the Superclasico after his side booked a derby clash with River.