One-Pot Diastereoselective Synthesis of Spiro[pyrimidine-5,8′-thiazolo[5,4- <i>f</i> ]quinoline]triones and Diimidazo-pyrazinyl-bis(1,3-dimethyl-2,4,6-trioxohexahydropyrimidine-5-ylium)dihydrate as Anticancer Agents

The development of nitrogen- and sulfur-containing heterocycles remains a central challenge in modern synthetic chemistry owing to their structural diversity and biological relevance. Herein, we report the synthesis of the ionic liquid (IL) 1-dodecyl-1-methylpiperidinium chloride ([C 12 mpip][Cl]) and, for the first time, its application as an efficient catalyst in an unprecedented divergent one-pot cyclization. The protocol enables the cyclization of 6-aminobenzothiazole with diverse aryl or heteroaryl aldehydes and 1,3-dimethylbarbituric acid in ethanol as a green solvent under reflux conditions. Apart from ortho -substituted and NH-unsubstituted heteroaryl aldehydes, the reaction proceeds with high regio- and diastereoselectivity to afford spiro[pyrimidine-5,8′-thiazolo[5,4- f ]quinoline]triones 4 ( a – l ) in yields of up to 94% and diastereomeric ratios exceeding >99:1 ( syn: anti ). Notably, the reaction outcome is governed by the aldehyde substitution pattern, enabling controlled access to structurally distinct fused heterocycles under identical conditions. The method constructs two new stereogenic centers and multiple σ-bonds in a single operation and is readily scalable to the gram scale with consistently high yields. All structures were confirmed by spectroscopic techniques and single-crystal X-ray analysis. Antiproliferative evaluation across six solid tumor cell lines identified compound 4l as a lead candidate, displaying uniform single-digit micromolar GI 50 values (1.22–7.40 μM) and potent activity against patient-derived glioblastoma (GBM6) cells (GI 50 = 2.40 μM). Compound 5b also exhibited consistent low-micromolar growth inhibition across multiple cancer cell lines. The operational simplicity, scalability, and promising biological profile facilitated gram-scale synthesis with yields of up to 94%.