Dihydropteridinones

Fluorous Synthesis of Dihydropteridinones by Microwave-Assisted Cyclative Cleavage... 

Fig. 31 Composition of dihydropteridinone ring system using q clative cleavage in fluorous-phase. Reagents and conditions a EtOAc, MeOH, THE, MW 150 °C, 15 min, sealed vials. Y = C, N, O R = Me, Et, i-Bu, Bn R = H, aromatic or heteroaromatic ring...

Dichloro-2( lff)-pyrazinones 273 Dihydropteridinones, fluorous synthesis, cyclative cleavage 113... 

Scheme 7.79 Generation of dihydropteridinones by cyclative cleavage from a fluorous tag.

As only small amounts of the hydrogenation products underwent spontaneous cyclization, the compounds were heated in a sealed vessel under microwave irradiation. Due to the low solubility of the cyclized products at room temperature, they precipitated upon cooling and could be easily collected by filtration. The desired dihydropteridinones were obtained in high purity and could be readily used to generate a more diverse library by subsequent N-alkylation [92],... 

Solid-phase synthesis of dihydropteridinones has been achieved from 4,6-dichloro-5-nitropyrimidine <00TL8177>. A series of ethyl 7-aminopteridine-6-carboxylate derivatives has been prepared in one step from the reaction of vicinal diamines as 13-dialky 1-5,6-diamino-2-thiouracils with diethyl ( )-2,3-dicyanobutenedioate <99JHC1317>. The relative binding affinities to human dihydrofolate reductase of new 2,4-diaminopteridine derivatives... 

The synthesis of N-alkylated dihydropteridinones 34 started with a displacement reaction of 4,6-dichloro-5-nitropyrimidine with a fluorous amino-ester (Scheme 23) [53]. The compounds formed 35 were then reacted with secondary amines to yield 36. The reduction of the nitro group of 36 was conducted by hydrogenation using Pd on charcoal as a catalyst. The cyclization reactions of 37 were promoted by microwave irradiation. The N-alkylation reaction of the cyclized products 38 with benzyl halides gave monobenzylated... 

FIGURE 1.6 Fluorous amino acid-facilitated synthesis of Af-aUcylated dihydropteridinones. 1.3.6.1.7 Fluorous Multicomponent Reactions... 

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