The shooting occurred shortly after 11:30 p.m. near the intersection of Central Avenue and Imperial Highway, a spokesperson for the Los Angeles Police Department said.
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The victim, who was followed off of the freeway by the shooter, suffered as many as five gunshot wounds from a pistol and was pronounced dead inside his vehicle, the LAPD said. He was identified only as a man approximately 50 years of age.
"We've reviewed some video, and so apparently there was a vehicle that was following close by as they exit," a police captain told reporters at the scene. "The vehicle pulls up next to him, shoots multiple times into the vehicle and flees."
The shooter fled eastbound on Imperial Highway in a dark-colored compact sedan, investigators said.
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The motive for the shooting was unknown.
Anyone with information about the incident is asked to call the LAPD's South Bureau Homicide Division at (323) 786-5100.