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| c. 580 BC |
| | Nebuchadnezzar builds the hanging gardens of Babylon, supposedly to comfort a homesick wife | |
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| c. 580 BC |
| | The synagogue, as a simple place of Jewish worship, develops during the Babylonian captivity | |
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| c. 550 BC |
| | The optimistic concept of the Messiah is part of the Jewish response to captivity in Babylon | |
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| 539 BC |
| | A Persian army captures Babylon and brings it into the empire of Cyrus the Great | |
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| 331 BC |
| | Moving northeast into Mesopotamia, Alexander again defeats Darius III (at Gaugamela), leaving Persia open to his advances | |
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| 323 BC |
| | Alexander, still only 33, dies in Babylon following a banquet | |
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| 312 BC |
| | Seleucia is founded as a new capital on the Tigris, eclipsing Babylon and recycling much of the older city as building material | |
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| 299 BC |
| | Seleucus founds Antioch as a Greek city on the trade route between Mesopotamia and Europe | |
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| c. 200 BC |
| | The oasis city of Palmyra acquires importance on the caravan route between Mesopotamia and the Mediterranean | |
| | Palmyra Fotofile CG
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| c. 100 BC |
| | The Parthians develop the site of Ctesiphon, on the east bank of the Tigris opposite Seleucia | |
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