Concise Synthesis of Tetrazole–Ketopiperazines by Two Consecutive Ugi Reactions

Abstract

A concise route for the synthesis of the novel compound class tetrazole–diketopiperazines was developed. The approach involves the use of two multicomponent reactions: the Ugi tetrazole four‐component reaction (4CR) and the classical intramolecular Ugi 4CR. The tetrazole–diketopiperazines comprise analogs of and are bioisosteric to bioactive diketopiperazines, which thus draws attention for novel bioactive compound design. This scaffold was produced to fill the screening deck of the European lead factory.

Isocyanide-based multicomponent reactions in the synthesis of heterocycles

“…Shaabani et al 255 188 188 205 Scheme 65 210 . It is worth noting that the best choice of base in the case of benzohydrazides was NaOAc, while Na 2 CO 3 was the most efficient base for reactions with benzothiohydrazide.…”

Groebke–Blackburn–Bienaymé multicomponent reaction: emerging chemistry for drug discovery

“…Commercially available 3-amino-6-chloropyridazine could also be used for further derivatisation. In this case, nucleophilic substitution reactions can give access to imidazo [1,2-b]pyridazines (13) with several substituents patterns in position 6 (Scheme 6, see also secondary transformations).…”

“…This reaction was further expanded by Ugi and Steinbrückner in 1961 by using amines to give a dipeptide-like backbone ( Fig. 1b; [10][11][12][13]). …”

“…The component variations, postmodifications and secondary transformations will also be discussed. For general information about MCRs, IMCRs and their applications in the synthesis of biologically relevant heterocycles, the reader is directed towards more comprehensive reviews and monographs [13,18,19,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. …”

Azidotrimethylsilane

“…208 It is also possible to synthesize tetrazole-fused ketopiperazines from an Ugi fourcomponent reactions. 209 Miscellaneous Reactions. The ring expansion of borolses to form 1,2-azaborinines is performed using azidotrimethylsilane.…”