Synthesis of Pyridodiazepinediones by Using the Ugi Multicomponent Reaction

Abstract

Benzodiazepines show a broad spectrum of biological activities. In an ongoing effort to extend molecular diversity in this type of systems, we developed a strategy for synthesizing3,4‐dihydro‐1H‐pyrido[2,3‐e][1,4]diazepine‐2,5‐dione compounds starting from 2‐hydroxynicotinic acid and by using an Ugi reaction as a key step in the synthesis. We opted to use 2‐isocyanophenyl benzoate instead of Armstrong's convertible isocyanide in this multicomponent reaction.

Synthesis of 1,4-Benzodiazepine-2,5-diones by Base Promoted Ring Expansion of 3-Aminoquinoline-2,4-diones

“…In contrast to the C3-benzyl and C3-alkyl derivatives 3d , 3e , 3j – 3l , the NMR spectra of the C3-phenyl-substituted products 3a – 3c and 3f – 3i indicated a single set of resonances. The conformational behavior is consistent with that observed in related 1,4-benzodiazepine-2,5-diones. ,,− …”

Crystal structure of 5-benzyl-8-bromo-2-methyl-1,3-oxazolo[4,5-c][1,8]naphthyridin-4(5H)-one

“…1). Commercially available 2-hydroxynicotinic acid 1 was converted to dihalonicotinic acid 3 via two sequential halogenation reactions (Van den Bogaert et al, 2010;Gero et al, 1989;Haché et al, 2002), after which a benzylamine substituent was introduced yielding the aza-anthranilic acid derivative 4. Next, ester compound 5 was prepared from intermediate 4 and tert-butyl glycinate using a standard coupling procedure.…”

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

“…Among the variety of heterocyclic acids used in Ugi-4CR [15–19 21–42] only a few of them in addition to bearing a simple pharmacophore core (group I, Scheme 1) are also characterized by the complexity and diversity of the skeleton itself gained through multi-step transformations (group II) [18–19 34–36] or allow for generating additional diversity through post-cyclization reactions (group III) [18,35–42]. Meanwhile the complexity of the acid skeleton can be achieved by MCR.…”