Traceless solid phase synthesis of 2-substituted pyrimidines using an ‘off-the-shelf’ chlorogermane-functionalised resin

Abstract

The parallel solid phase synthesis of an 18-member library of 2-substituted pyrimidines is described using a chlorogermane-functionalised resin. The success of the key Pinner-type condensations between a resin-bound enaminone and an array of amidine hydrochlorides highlights the stability of arylgermane linkers (cf. arylsilanes) towards strongly basic/nucleophilic conditions.

The development of a ‘safety‐catch’ arylgermane for biaryl synthesis by palladium‐catalysed germyl‐stille cross‐coupling

“…In the context of a program to develop arylgermane-based linkers for phase-tagged synthesis of heterocyclic libraries 61,62 and of high purity oligothiophenes 63,64 for 'plastic electronic' applications, we required a 'safety-catch' linker that would allow cleavage from the phase-tag with concomitant C-C bond formation. 65 It was envisaged that such a method of cleavage in which the arylgermane, following 'activation' of the safety-catch, could be enticed to participate in Pd(0)-catalysed cross-coupling with aryl halides would constitute a powerful method of diversification via biaryl formation in these and other applications (Scheme 1).…”

Microwave‐assisted one‐pot synthesis of functionalized pyrimidines using ionic liquid

“…Consequently, synthetic methodologies for the synthesis of pyrimidines or pyrimidine‐fused compounds are of paramount importance, particularly in the medicinal and agrochemical areas [14, 15]. Although some pyrimidine synthetic routes have been known for a long time, the development of alternative and more efficient strategies is of considerable relevance [16–19].…”

An efficient one-pot synthesis of polyfunctionalized 2H-pyrroline derivatives by reaction of β-enaminocarbonyls, arylglyoxals and amines

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Multi-component reactions (MCRs), especially threecomponent reactions, offer significant advantages over conventional linear-type syntheses, because the combination of the reaction components to generate new products in a single step is easy and economic [12,13].β-Enaminocarbonyls are important compounds used for selective alkylation and acylation of carbonyl compounds and valuable intermediates for the synthesis of biologically active compounds [14][15][16]. These compounds are useful starting points for the preparation of a variety of heterocyclic compounds [17] utilized for synthesis of pharmaceuticals [18] and are building blocks for amino acids [19], peptides [20] or alkaloids [21].

Designing of multi-component reactions in water is another attractive area in chemistry, because water is a cheap, safe and an environmentally benign solvent [22].

Multi-component reactions of arylglyoxals and enaminocarbonyls in the presence of different nucleophiles have been recently reported for synthesis of polyfunctionalized pyrroles [23][24][25].

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“…β-Enaminocarbonyls are important compounds used for selective alkylation and acylation of carbonyl compounds and valuable intermediates for the synthesis of biologically active compounds [14][15][16]. These compounds are useful starting points for the preparation of a variety of heterocyclic compounds [17] utilized for synthesis of pharmaceuticals [18] and are building blocks for amino acids [19], peptides [20] or alkaloids [21].…”