Cyanoacetylation of 5-Aminopyrazole: Synthesis of 2-(1-Aryl-4- substituted pyrazolo[3,4-d]pyrimidin-6-yl)acetonitrile Derivatives

Abstract

N1 -cyanopyrazoles were cyanoacetylated with a mixture of cyanoacetic acid and acetic anhydride. Cyclization with POCl 3 gave 4-chloro-pyrazolo[3,4-d]pyrimidine derivatives. From the reaction with hydrazine and arylhydrazines, the hydrazinyls and their oxidized forms, the azo products, were obtained. The structure of the compounds obtained has been confirmed by 1 H and 13 C NMR spectroscopy.

Synthesis of some new amide-linked bipyrazoles and their evaluation as anti-inflammatory and analgesic agents

“…It should be noted here that heating the reaction mixture at 95 C for 30 min. as previously reported 38 resulted in a black tar which was very difficult to work up or purify, whereas, heating at 50 C for a longer time gave a pure product in a good yield. Condensation of 3 with aromatic aldehydes in boiling ethanol containing a catalytic amount of piperidine afforded the corresponding acrylamides 4a-c. 1 H-NMR of the latter compounds revealed presence of double the number of the expected protons indicating presence of these compounds as a mixture of E and Z isomers.…”

“…In Scheme 1, the starting 5-amino-3-methylsulfanyl-1Hpyrazole-4-carbonitrile 2 was prepared as previously described 32 . Synthesis of the cyanoacetamide derivative 3 was achieved by pouring the pyrazolecarbonitrile 2 into a solution of the cyanoacetylating reagent (cyanoacetic acid and acetic anhydride) followed by heating the mixture at 50 C for 5 h modifying the reaction conditions previously reported for synthesis of allied compounds 38 . It should be noted here that heating the reaction mixture at 95 C for 30 min.…”

Enamines in Heterocyclic Synthesis: Route to Aminopyrazolopyrimidines and Arylpyrazolopyrimidiens Derivatives

“…A key advantage of modern, scientific microwave apparatus is their ability to control reaction conditions precisely, by monitoring temperature/pressure, reaction times and ease of isolation of the products after easy work-up [11,12]. In conjunction to our interest in the chemistry of enaminonitriles [13][14][15][16][17], we report here results of our work aimed at developing efficient environmentally friendly syntheses for several targeted pyrazolopyrimidines utilizing enamines 2,4 and 6a,b as starting materials. In our chemical reactivity studies described here, we principally employed the intermediate 6b due to their easy preparation and good yield of reactions.…”