Quinazoline-2,4-diones, solid-phase synthesi

Tripeptides with N-terminal anthranilic acid part were used as starting materials in the solid-phase synthesis carried out on TentaGel resin to prepare 1,4,11,1 l -tetrahydro-2//-pyrazino[2,l-3]quinazoline-3,6-diones with various N-l and N-3 substituents <2003EPP1471066>. Tandem cyclization from [6+0] atom fragments took place in the solid-phase synthesis of 143 from 142. Intermediate 141 was built on bromoacetal resin (Scheme 17) <1998JOC3162>. 

Gordeev MF, Hui HC, Gordon EM, Patel DV, A general and efficient solid phase synthesis of quinazoline-2,4-diones, Tetrahedron Lett., 38 1729-1732, 1997. 

Castelhano et al. described the solid-phase synthesis of quinazoline-2,4-diones 313 based on the chemistry of acyl azides. Phthalic acid was immobilized on a PEG4-PS resin and converted into acyl azide 310 with DPPA and triethylamine in toluene. Curtius rearrangement, followed by reaction with a primary amine and subsequent cyclocleavage with K2CO3 gave quinazoline-2,4-diones 313 in good yield (Scheme 3.48). 

Gorl997b Gordeev, M.F., Hui, H.C., Gordon, E.M. and Patel, D.V., A General and Efficient Solid Phase Synthesis of Quinazoline-2,4-diones, Tetrahedron Lett., 38 (1997) 1729-1732. 

Goul996 Gouilleux, L., Fehrentz, J.-A., Wintemitz, F. and Martinez, J., Solid Phase Synthesis of Chiral 3-Substituted Quinazoline-2,4-diones, Tetrahedron Lett., 37 (1996) 7031-7034. 

A recent example of the parallel synthesis of different quinazoline-2,4-dione derivatives (46) demonstrates how to combine the advantages of fluorous synthesis with those of solid-phase chemistry without using expensive perfluorinated solvents [22] (Scheme 3.22). In the beginning, a fluorous benzyl alcohol (47) is adsorbed on fluorous reversed-phase silica gel (FRPSG). Then, in a sequence of splits and reactions, the linker group, which remains bound to the FRPSG by fluorophilic interactions, is converted into a library of differently substituted carboxamido-urethanes (48). These are cyclized and the liberated quinazoline-2,4-diones (46) are eluted from the support with the fluorophobic solvents water and CHjCN/... 

Fused pyrimidine-2,4-diones are important heterocyclic pharmacophores examples include natural purine bases, alkaloids, and pteridines. Benzo derivatives in this series (quinazoline-2,4-diones) bear ample precedence as potent ligands and inhibitors of receptors and enzymes of pharmaceutical interest. Based on these precedents, Gordeev et al. reported a solid-phase protocol for the synthesis of fused pyrimidine-2,4-diones. 

Smil996a Smith, A.L., Thomson, C.G. and Leeson, P.D., An Efficient Solid Phase Synthetic Route to 1,3-Disubstituted (1H,3H)-Quinazoline-2,4-diones Suitable for Combinatorial Synthesis, Bioorg. Med. Chem. Lett., 6 (1996) 1483-1486. 

---