An alternative synthesis of pyrimido[4,5-b]quinoline-4-ones via metal-free amination in water and Vilsmeier–Haack cyclization

Two-step synthesis of pyrimido[4,5-b]quinoline-4-ones is described from 2-chloroquinoline-3-carbonitries via amination and cyclization reactions, respectively. The amination reactions proceeded much faster in water via simple SNAr displacement reactions of chlorine. The cyclization reactions using Vilsmeier reagent at 60 °C gave the best yield of the products. The isolation of starting compound from the reaction of cyclized product with I2/K2CO3 provided further chemical proof of the structure of the cyclized product. Plausible mechanism for cyclization is proposed.