Mohammad Javad Zarif said the West "cannot entertain illusions" of Iran completely ending its uranium enrichment program.
Speaking in Tokyo, he also reiterated that his country is not going to halt construction of a heavy-water nuclear reactor.
"We are not going to close it. We are not going to dismantle it. We are not going to close or dismantle anything, that is our red line," he said at a news conference before meetings with the Japanese prime minister and foreign minister.
"But we will address proliferation concerns that people may have."
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Iran is trying to negotiate a deal with the US and five other global powers to scale back its nuclear program in exchange for a lifting of sanctions. An interim agreement was reached in November, and the parties have begun negotiating a final deal.
Zarif said some appear to be trying to torpedo the talks, making a veiled reference to the crowd at Nethanyahu's speech to the American Israel Public Affairs Committee, "but I don't think they will succeed because there is no other game in town. That's the only game. That's the only reasonable game."