Heterocyclic Synthesis with Nitriles: Synthesis of Pyrazolopyrimidine and Pyrazolopyridine Derivatives

Abstract

The reaction of N 1-substituted-5-amino-4-cyanopyrazoles with malononitrile and diethylmalonate occurs with formation of 6-substituted pyrazolo[3,4-d]pyrimidines, and pyrazolo[3,4-b]pyridines respectively. The structures of the products and conceivable mechanisms are discussed.

Synthesis of 3-indolylazoles and meridianin derivatives from indolyl enaminonitriles

“…Following our interest in the chemistry of -enaminonitriles, [10][11][12][13] in this manuscript we describe our most recent results that explore the potential of 3(2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate in the synthesis of 5´-cyanomeridianin C, G and 3-heteroarylindoles. Commercially available indole and indole-3-carboxaldehyde were employed as the starting materials giving access to the meridianin analogs 4a-c in a straightforward three-step synthesis following the Bredereck approach 7 (Scheme 1), and to 14 from one-pot synthesis as shown in Scheme 3.…”

“…This configuration has important consequences in the crystal packing as it permits the existence of a vast network composed of strong and highly directional hydrogen bonding interactions ( As anticipated, the treatment of compound 3a with p-methoxyphenylhydrazine, in refluxing ethanol, in a basic medium, afforded as single product only pyrazole 7 (Scheme 1). The structure of the pyrazole 9 was excluded due to the absence of the typical signals of cyano groups in both the FT-IR and 13 C NMR spectra. The 1 H NMR of compound 7 showed all the expected signals which was not sufficient to differentiate between structures 7 and 8.…”

“…Direct conversion of 3a-c into 5´-cyano meridianin C and meridianin G derivatives 4a-c, involving the formation of the 2-aminopyrimidine ring, was achieved in 70-78% by treatment with guanidine hydrochloride in the presence of anhydrous potassium carbonate (Scheme 1). The structure of compounds 4a-c was established on the basis of elemental analysis, IR, mass, 1 H and 13 C NMR spectral data studies (cf. Experimental Section).…”

“…FT-IR spectra were registered on a Perkin Elmer FT-IR 1600 using Nujol emulsions between NaCl plates. 1 H NMR (300 MHz) and 13 C NMR (75.4 MHz) spectra were recorded on a Varian Unity Plus Spectrometer at 298 K. Chemical shifts are reported in ppm relative to solvent peak or TMS; coupling constants (J) are given in Hz. Double resonance, HMQC (heteronuclear multiple quantum coherence) and HMBC (heteronuclear multiple bond correlation) experiments were carried out for complete assignment of 1 H and 13 C signals in the NMR spectra.…”

“…The structure of compound 10 was readily established from 1 H NMR data, which revealed all the expected protons of the indole moiety alongside with a singlet at 8.59 ppm for the H-4 of the pyridinone ring and a NH broad signal at 13.10 ppm. Two signals due to CN groups were found in the 13 C NMR spectrum at 115.44 and 116.96 ppm. The formation of the pyridine-3,5-dicarbonitrile 10 from the reaction of 3a with malononitrile is assumed to take place through the sequence depicted in Scheme 2.…”