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

Polymer-Supported Synthesis of Various Pteridinones and Pyrimidodiazepinones

“…The literature described methodologies leading to the synthesis of 7,8-dihydropteridin-6(5 H )-ones based on various synthetic approaches comprising either traditional solution-phase synthesis or solid-phase synthesis ( Figure 2 ) [ 1 , 2 , 8 , 19 , 20 , 21 , 22 , 23 ]. The most convenient solution-phase synthesis of dihydropteridinone heterocycle consists of the cyclization of appropriately substituted pyrimidine with modified amino ester.…”

“…In 2000, Baxter et al published the first solid-phase synthesis of dihydropteridinones using Wang resin ( Figure 3 ) [ 19 ]. This work was followed by Metzger et al, who used ArgoGel resin instead [ 21 ].…”

Design, Construction, and Screening of Diversified Pyrimidine-Focused DNA-Encoded Libraries

“…As evidenced in the literature, the presence of the nitro group substantially enhances the reactivity of the C4chloride, leading to regioselective S N Ar chloride displacement at the C4 position with a regioisomeric excess exceeding 90%. 24,25 In this context, the DNA barcodes were preferentially attached to the C4 position of P-II and P-III, resulting in the formation of DNA-linked products 9-1 and 9-2. During the cycle 2 chemical synthesis using 568 amines, both the C6chloride in 9-1 and the C2-chloride in 9-2 exhibit higher reactivity compared to their counterparts (5-1 and 5-2, respectively); the S N Ar substitution could proceed at room temperature.…”

Regioselective Control of the SNAr Amination of 5-Substituted-2,4-Dichloropyrimidines Using Tertiary Amine Nucleophiles

“…Indeed, with many amine nucleophiles, this regioselectivity is so good that the accompanying experimentals often fail to acknowledge the possible presence of a minor product from competing substitution at C-2. Where the ratio for C-4 compared to C-2 substitution of 2,4-dichloro-5-nitropyrimidine 1 has been measured with sterically unencumbered amines, ratios between 9:1 to 19:1 are observed. ,− As the initial reaction of longer synthetic sequences, this reaction dictates the overall synthetic strategy. As the C-4 regioselectivity is not always desirable, effort has been given to the use of a Lewis acid (such as ZnCl 2 ) to direct amine nucleophiles toward preferential substitution at C-2 of the pyrimidine. , Here, we report a simple alternative toward this same objective: the use of a tertiary amine as the S N Ar nucleophile.…”