Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

Abstract

SummaryThe three possible structural isomers of 4-(pyridyl)pyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their corresponding cycloimmonium bromides. In the case of 4-(3-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine the quaternization reactions occur as expected at the pyridine nitrogen atom leading to pyridinium bromides and consequently to new indolizines via the corresponding pyridinium N-ylides. However, in the case of 4-(2-pyridyl)pyrimidine the steric hindrance directs the reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new indolizines were structurally characterized through NMR spectroscopy. The X-ray structures of two of the starting materials, 4-(2-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine, are also reported.

Synthesis and spectroscopic properties of novel indolizines and azaindolizines

“…[27][28][29][30] Usually, this multistep process starts with the preparation of N-heterocyclic quaternary salts with -halo carbonyl compounds, in situ conversion into corresponding heterocyclic N-ylides in the presence of an inorganic or organic base and 3+2 dipolar cycloaddition reactions of heterocyclic N-ylides with electron-deficient alkynes or alkenes. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] Our group has developed a simple one-pot, multicomponent synthetic strategy towards N-bridgehead heterocyclic compounds based on the consecutive quaternization of the N-heteroaromatic compound, in situ generation of the heterocyclic N-ylide, 3+2 dipolar cycloaddition reaction to an electron-deficient alkyne and aromatization sequence, using an epoxide as solvent and acid scavenger. [46][47][48][49][50][51][52][53][54][55] A range of new indolizines and azaindolizines were synthesized via 3+2 dipolar cycloaddition reactions of cycloimmonium ylides, generated from the various N-heterocycles such as pyridine, quinoline, isoquinoline, pyridazine, pyrimidine, phthalazine and benzimidazole derivatives with diverse phenacyl bromides, alkyl bromoacetates, 3-(2-bromoacetyl)-2H-chromen-2-one and electrondeficient alkynes.…”

Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis

“…As a result, it was of interest to prepare analogous compounds containing a pyrroloazine directly attached to the C-4 position of a sydnone ring. From a survey of the literature data [6–15] and based on our previous findings [16–19] it was concluded that the heterocycle in the pyrroloazine series most suitable for this study would be indolizine ( 2 ).…”