The comments by Ayatollah Ali Khamenei, who repeatedly has backed the Islamic Republic's negotiators amid criticism from hard-liners, may give his diplomats little room for concessions ahead of the June 30 deadline.
They also directly challenge the US, especially his demand that Iran only will sign a final deal if economic sanctions are first lifted.
Iran's parliament already has passed a bill that, if ratified, will ban access to military sites, documents and its scientists as part of any future deal. The bill must be ratified by the Guardian Council, a constitutional watchdog, to become a law.
"We don't accept 10-year restriction. We have told the negotiating team how many specific years of restrictions are acceptable," Khamenei said. "Research and development must continue during the years of restrictions."
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Khamenei accused the US of offering a "complicated formula" for lifting sanctions. He added waiting for the UN's International Atomic Energy Agency to verify its cooperation would take too long.
"Lifting sanctions can't depend on implementation of Iran's obligations," he said.
Khamenei also said he rejects any inspection of military sites or allowing its scientists to be interviewed. Iran's nuclear scientists have been the targets of attacks before both inside the Islamic Republic and elsewhere.
In a statement Sunday, the US State Department said inspections remain a key part of any final deal.
Tehran is negotiating with the US, Russia, China, Britain, France and Germany over its contested nuclear program. The talks are focused on reaching a final accord that curbs Iran's nuclear program in return for the lifting of economic sanctions.