The flames broke out just after 10:15 a.m. inside an apartment on the third floor of the building on West 87th Street near Amsterdam Avenue.
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The fire was placed under control a short time later.
A 71-year-old man was found unconscious and unresponsive inside apartment 3F.
He was pronounced dead at the scene.
One of the injuries was described as serious, while the other was considered minor.
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Both of the injured victims are believed to be residents.
The cause of the fire is under investigation.
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