Relations between Isaac and John II were cordial at first, but began to deteriorate, so that by 1130 they had become estranged. The reasons for this are left unexplained by the sources; Niketas Choniates and John Kinnamos simply report that Isaac had set his sight on the throne. Possibly the onset of the rift between the brothers was in 1122, when John raised his own firstborn son, Alexios, to co-emperor, thus superseding Isaac. In 1130, Isaac became involved in a conspiracy against John at a time when the latter was away from Constantinople, campaigning against the Seljuk Turks of the Sultanate of Rum. The conspiracy was uncovered, but Isaac and his two sons managed to flee Constantinople and find refuge at the court of the Danishmendid emir Ghazi () at Melitene.