Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

Abstract

The syntheses of various pyrimidinones as potentially bioactive products by means of the highly controlled continuous-flow retro-Diels–Alder reaction of condensed pyrimidinone derivatives are presented. Noteworthy, the use of this approach allowed us to rapidly screen a selection of conditions and quickly confirm the viability of preparing the desired pyrimidinones in short reaction times. Yields typically higher than those published earlier using conventional batch or microwave processes were achieved.

Newly Developed CK1-Specific Inhibitors Show Specifically Stronger Effects on CK1 Mutants and Colon Cancer Cell Lines

“…Introduction of the thioxo group (compounds 8−14) followed the procedure of Xu and Yadan using phenyl thionochloroformate [28]. Compound 8 as well has been described in the literature [29]. The synthesis of the benzothiazole-linker was already described by García-Reyes and Witt et al [15].…”

Continuous‐Flow retro‐Diels–Alder Reaction: A Process Window for Designing Heterocyclic Scaffolds

“…Our previous investigations on the CF rDA reactions of condensed pyrimidinone derivatives revealed that the CF approach is superior to existing conventional batch methods. [9] In this work, starting materials were selected with the aim of testing the viability of the proposed CF rDA protocol with more complex fused pyrimidinone moieties, and also of investigating molecules that have never been subjected to rDA reactions under batch conditions. We started our study with readily available aminocarboxamides 1a-1d, which were prepared by known literature approaches.…”

“…It is important to note that toluene is known to be an effective solvent under superheated CF rDA conditions. [9,33] This effect is even more pronounced when MeOH is used as a cosolvent. The transformation of diexo-methylene-bridged 2-spiroquinazolinone 8 is illustrative.…”

“…We recently revealed the potential of the use of continuous‐flow (CF) technology for the synthesis of various functionalized pyrimidinone systems through rDA reactions . Our interest in CF processes can be explained, at least in part, by the number of potential advantages that CF processes have over traditional batch chemistry.…”

“…[8] We recently revealed the potential of the use of continuousflow (CF) technology for the synthesis of various functionalized pyrimidinone systems through rDA reactions. [9] Our interest in processes. These results were achieved through careful optimization of the reaction parameters.…”