A novel protocol for rapid assemble of quinoxalinones framework has been demonstrated. This method incorporated with soluble polymer support provides a convenient approach for diversification of heterocyclic compounds and for easy purification via facile precipitation from reaction matrix. The key transformation of this study involves in situ reduction of aromatic nitro compound, tandem lactamization concomitant with traceless cleavage of the polymer support under microwave irradiation in a one-pot fashion. Moreover, forward synthetic routes were introduced to maximize complexity of the master intermediate on which further chemical elaboration was applied. The strategy is envisaged to apply for establishment of drug-like small-molecule libraries for high-throughput screening.