Synthesis and dynamic 1H NMR study of pyrazolo substituted pyrrolo[2,3-d]pyrimidines via a regioselective heterocyclization

Abstract

A new series of pyrrolo[2,3-d]pyrimidine derivatives substituted with pyrazolone were designed and prepared, by the three-component reaction of pyrazolone derivatives, arylglyoxal and 6-aminouracil derivatives in ethanol at reflux. The direction of heterocyclization has confirmed and the structure of final products were identified spectroscopically (IR, 1H- and 13C-NMR, and EI-MS). The significant advantages of this protocol include simplicity, regioselectivity, existence of numerous hydrogen bonding possibilities in product, good yields and catalyst-free approach. When the uracil is 6-amino-1,3-dimethyluracil, the product exists as two tautomers at room temperature. The dynamic NMR effects are observed in the 1H NMR spectra. The calculated free-energy of activation (ΔG≠) for prototropic tautomerism is about 68 ± 2 kJ mol−1.