The Ottomans had been trying to conquer the Byzantine Empire since the early 14th century. Osman Ghazi had laid a siege to Nicaea in 1301. He annihilated the Byzantine army but failed to capture Nicaea because of the arrival of a mercenary army of 8000 troops led by Roger de Flor. Osman was succeeded by his son Orhan in 1324. Orhan captured several cities belonging to the Byzantines in northwest Turkey. He took advantage of the civil war, which followed the death of the Byzantine Emperor Andronikos III Palaiologos in 1341, and captured the peninsula of Gallipoli which he fortified to gain control of Dardanelles. Orhan’s son Murad I became the sultan in 1362 and continued to pursue the policy of expanding the frontiers of the Ottoman Empire.
When Murad I was killed in the Battle of Kosovo in 1389, the sultanate passed into the hands of his son Bayezid I Yildirim, who took the title Sultan-i Rum (Rum being an old oriental name for the Roman Empire). Bayezid had his brothers strangled to prevent any disputes regarding his succession. He blamed the death of his father to Byzantine and Serbian treachery, and was determined to conquer Constantinople. In 1394, he laid siege to Constantinople and ordered the Byzantine emperor to surrender. The Byzantines pleaded before Pope Boniface IX who called a crusade to vanquish the Ottoman forces. Sigismund of Luxembourg, the King of Hungary, who later became the Holy Roman Emperor, and knights from France, Germany, Venice, and Genoa, answered the pope’s call. But Bayezid managed to defeat the crusader forces in the Battle of Nicopolis and then he resumed the blockade of Constantinople.
Bayezid's heavy artillery could not cause much damage to the ancient wall which protected Constantinople but he would have found a way to enter the city if he had not been forced to lift the seize in 1402 due to the appearance of the massive army of Tamerlane, the Prince of Destruction, who had fought several wars in Asia, Africa, and Europe and was never defeated.
Tamerlane and Bayezid had been insulting each other in letters for sometime. In one of his letters, Tamerlane wrote: “Believe me, you are but pismire ant: don't seek to fight the elephants for they'll crush you under their feet. Shall a petty prince such as you are contend with us? But your rodomontades (braggadocio) are not extraordinary; for a Turcoman never spake with judgement. If you don't follow our counsels you will regret it.” Tamerlane’s army marched into Syria in 1400, killing most of the inhabitants of Aleppo and Damascus. They sacked Baghdad in 1401, slaughtering 20,000 people, and on July 20, 1402, they marched into Anatolia where they were confronted by Bayezid’s forces. But Bayezid was defeated and captured. He subsequently died in Tamerlane’s prison.
With Bayezid death, there was a period of respite for the Byzantine Empire since the Ottomans became entangled in a succession related civil war. Four of Bayezid's sons, Süleyman Çelebi, İsa Çelebi, Mehmed Çelebi, and Musa Çelebi, were the main contenders for the throne. Mehmed Çelebi was victorious. At his coronation in 1413, he took the name Mehmed I. When Mehmed I died in 1421, the power went to his son Murad II who began his reign by besieging Constantinople. But the Byzantines managed to coerce Murad’s younger brother Küçük Mustafa, who was only thirteen years old, to rebel against the sultan and besiege Bursa. Murad was forced to abandon the siege of Constantinople and rush to Bursa to deal with his rebellious brother. He defeated Mustafa’s army and executed him.
In 1451, Murad II was succeeded by his son Mehmed II who achieved the dream of his ancestors by conquering Constantinople in 1453. After the conquest, Mehmed II took the title, Qayser-i Rum (the Caesar of the Roman Empire). According to some historical accounts, Mehmed II used to say: “I have conquered the New Rome. Now it is time to conquer the Old Rome.”