Arriving in Vienna for the negotiations aimed at drafting the text of an accord ahead of a July 20 deadline, Iran's foreign minister said "a lot of effort" was still needed.
"If there are differences of opinion, which definitely exist, we will spend time to resolve them," Mohammad Javad Zarif told Iranian media after touching down in the Austrian capital.
A senior US official said that the talks between Iran and the five permanent members of the UN Security Council plus Germany would be "very, very difficult."
She added that optimism raised in some quarters that a deal was within reach has "gotten way out of control".
The six powers and Iran want to transform an interim deal struck in Geneva in November into a permanent one by the time a six-month freeze of certain nuclear work by Iran ends on July 20.
In return the Islamic republic, which denies wanting the bomb and says its aims are purely peaceful, wants all UN and Western sanctions lifted.
If the negotiators can manage to get a deal, this could finally resolve a standoff that has been simmering and threatening to escalate into conflict for the past decade.
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