West Ham had seen a second-string team embarrassed 5-0 at Nottingham Forest in the FA Cup on Sunday, but even the return of several first-team players could not prevent a mauling by City's ruthless forwards in the semi-final first leg.
A smartly taken brace from Negredo and a goal from the marauding Yaya Toure put City 3-0 up, with Negredo completing his hat-trick in the second half before Edin Dzeko sealed victory with two goals of his own.
For injury-ravaged West Ham, meanwhile, focus will reluctantly return to the fight to haul themselves out of the Premier League relegation zone.
West Ham manager Sam Allardyce made eight changes to the team thrashed at Forest, handing a debut to new loan signing Roger Johnson, while Toure and Vincent Kompany were among the returning players in a strong City XI.
Speaking ahead of the game, Allardyce admitted that a draw would be an ideal result, but the visitors quickly found themselves overrun.
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