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A versatile solid-phase method for the synthesis of various substituted 2-amino-4(3H)-quinazolinones with two- and three-point diversity is described. The synthesis commenced with the generation of polymer-bound S-methylisothiourea followed by N-acylation with different substituted o-nitrobenzoic acid. Finally, reduction of the nitro group triggered intramolecular cyclization via formation of guanidine to afford 2-amino-4(3H)-quinazolinone and its derivatives in high yields and purities.

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A versatile method for the solid phase synthesis of quinoxalines has been developed. Polymer-linked 2-nitrophenyl carbamate is treated with a-bromoketones followed by reduction of the nitro group, which underwent spontaneous intramolecular cyclization to afford polymer bound quinoxalines. Finally acidolytic cleavage gave the desired compounds via aerial oxidation in high yields and good purities.In recent years solid phase synthesis of combinatorial libraries has emerged as a powerful tool for accelerating lead discovery in pharmaceutical research. This offers the opportunity of synthesizing compounds via novel routes, thereby providing structures with high chemical diversity. Intense synthetic efforts, and different synthetic approaches have been reported for several pharmacologically active heterocyclic systems. 2 Among the various classes of heterocyclic compounds, quinoxalines form an important component of pharmacologically active compounds. Quinoxaline ring is a part of various antibiotics such as Echinomycin, Levomycin and Actinoleutin 3,4 that are known to inhibit growth of Grampositive bacteria and are active against various transplantable tumors. 5 In addition quinoxaline derivatives are also associated with a wide spectrum of biological activities ranging from anthelmintic and anticancer 6 to antimicrobial, antifungal, and antidepressant. 7,8 Surprisingly, despite being an interesting class of compound, its synthesis on solid phase has not yet been well established though few reports dealing with the solid phase synthesis of quinoxalinones 9 and tetrahydro quinoxalines 10-13 have been reported. The solid phase synthesis for quinoxaline, described by Wu et al., 14 deals with its synthesis on SynPhase Lanterns, however, in their method quinoxalines were obtained predominantly as a mixture of two isomers. While the manuscript was under preparation, a paper by Mantellini et al. appeared dealing with the solid phase synthesis of quinoxaline from N=N-polymer bound 1,2-diaza-1,3-butadiene but the yield of the reaction were in the range of 15-31% only. 15 The work is based on their previous studies involving synthesis of quinoxaline both on solid phase as well as in solution phase. 16 Here we wish to report an efficient methodology for the solid phase synthesis of isomerically pure quinoxalines of high purity. To our knowledge this is the first report of synthesis of quinoxalines on solid phase. The solid phase synthesis of quinoxalines is outlined in Scheme 1 (Route A and B).Monitoring the progress of reactions on solid phase by single bead FTIR and cleavage of numerous 2-5 mg of resin bound samples with subsequent LC-MS analysis of the resultant products accompanied each step during optimization of the reaction conditions. The final compounds were subjected to purification using high throughput LC-MS (Lachrom 8000; Merck) and characterized by 1 H NMR.In the first step, o-nitrophenylisocyanate was loaded on to the Wang resin [Copolymer (styrene-1%DVB) Novabiochem, bead size 200-400 mesh; 1.13 mmol/g)] in th...

Application of Modified Pictet-Spengler Reaction for the Synthesis of Thiazolo-and Pyrazolo-quinolinesTetrahedron 2006, 62, 3228-3241.

Fused pyridine derivatives R 0450 Application of Modified Pictet-Spengler Reaction for the Synthesis of Thiazoloand Pyrazolo-quinolines. -The amines (II) and (IV) are found to be useful substrates. Their condensation with aldehydes provides a novel approach to the target compounds which are of biological interest. -(DUGGINENI, S.; SAWANT, D.; SAHA, B.; KUNDU*, B.; Tetrahedron 62 (2006) 14, 3228-3241; Div. Med. Chem., Cent. Drug Res. Inst., Lucknow 226 001, India; Eng.) -Jannicke 30-162