A traceless and efficient solid-phase synthetic strategy was developed for the construction of thiazolo[4,5-<i>b</i>] pyridin-7(4<i>H</i>)-one derivatives. The synthesis was initiated on Merrifield resin and proceeded through a five-step sequence, with each transformation monitored in real time using ATR-FTIR spectroscopy. This approach enables controlled and modular introduction of structural diversity. A focused library containing three points of diversification was successfully constructed, affording a total of 60 derivatives. Stepwise yields ranged from 72% to 87%, demonstrating excellent synthetic efficiency and robustness.