Solid-phase synthesis of N-9-substituted 2,8-diaminopurines

Solid-Phase Synthetic Strategies for the Preparation of Purine Derivatives

“…C 2 immobilization was also described to prepare the purine scaffold by the cyclization of solid-supported pyrimidine derivatives. 17 The nonregioselective amination of the starting 2,4-dichloro-5-nitropyrimidine 18 also required the solutionphase premodification and the separation of the key building block 19 from the mixture of two isomers (Scheme 4). After compound 19 was immobilized on the resin, the reduction of the nitro group was performed using sodium dithionate.…”

Synthesis of aminothiazoles: polymer-supported approaches

“…67 The amino-functionalized polystyrene resin 85 was acylated with an acid-cleavable linker, 4-(4 0 -formyl-3 0 -methoxy)phenoxybutyric acid, to obtain the aldehyde 86 (Scheme 16). 68 A resin-bound secondary amine 87 was generated by reductive alkylation of a series of primary amines (R 1 NH 2 ) with 86. Subsequently, the reaction of 87 with different acylisothiocyanates gave the N-acyl thioureas 88.…”

Combined solution-phase and solid-phase synthesis of 2-amino-7,8-dihydropteridin-6(5H)-ones

“…A solid-phase strategy is preferable for slow reactions where a large excess of reagents can be used to drive the transformation to completion with the excess of reagents easily being removed by washing with solvent. [2][3][4] Dihydropteridinones have a well exemplified history as biologically active molecules, for example, as kinase inhibitors 5,6 and as inhibitors of the RNA interference pathway in human cells. 7 The dihydropteridinone scaffold has been named a privileged heterocyclic ring system.…”

“…Derivatization of 1 with an amino-acid methyl ester at 0°C gave the two pyrimidine regioisomers 2 and 3 in a ratio of about 9:1, respectively (Scheme 1). 4 Separation of the desired regioisomer 2 from 3 was easily achieved by chromatography. This chromatographic purification necessitates that this step be carried out in solution and it resulted in high purity levels of the substituted 2-amino-7,8-dihydropteridin-6(5H)-ones at the end of the subsequent solid-phase synthesis.…”

“…Sodium hydrosulfite in a 1:1 mixture of water and 1,4-dioxane was ultimately chosen as the preferred reduction condition. 4 This reaction works efficiently under basic conditions, but the use of a variety of bases and reagent concentrations had to be investigated to minimize the formation of undesired by-products. The use of ammonium hydroxide as a base in conjunction with a low concentration of sodium hydrosulfite facilitates clean nitro group reduction, but the low reagent concentration necessitates the use of two reduction cycles to drive the reaction to completion.…”