Chemistry of substituted pyrazolo[1,5-a]pyrimidines. Part 5. 7-Oxo-6-[pyrazol-3′(5′)-yl]-4,7-dihydropyrazolo[1,5-a]pyrimidines from 6-ethoxycarbonyl-7-(2-dimethylaminovinyl)pyrazolo[1,5-a]-pyrimidines: elucidation of the reaction mechanism through NMR spectroscopy and X-ray diffraction analysis

Abstract

The reaction of 6-ethoxycarbonyl-7-(2-dimethylaminovinyl)pyrazolo[1,5-a]pyrimidines 1a,b with hydrazine hydrate in acetic acid solution gave rise to 7-oxo-6-[pyrazol-3′(5′)-yl]-4,7-dihydropyrazolo [1,5-a]pyrimidines 3a,b, a result very similar to the intramolecular cyclization previously reported for the corresponding 6-acetyl derivatives 1c,d. Treatment of compounds 3a,b with dimethyl sulfate gave rise to a mixture of the N-methyl derivatives 4a,b and 5a,b whose structures have been unambiguously established on the basis of NMR spectroscopy and confirmed by the X-ray structure of compound 4a. The same reaction carried out with methylhydrazine led to a mixture of 6-(1′-methylpyrazol-3′-yl)-7-oxo- 6a,b and 6-(1′-methylpyrazol-5′-yl)-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine 7a,b in which the former were predominant. When the reaction was carried out in ethanol, a different regioselectivity was observed leading to the isolation of the open-chain intermediate compounds 11–13 which in turn give rise, predominantly, to the pyrazolopyrimidine derivative 7a. A reaction pathway based on the X-ray structure of compound 11 is proposed.