An Unequivocal Synthesis of 2‐Aryl Substituted 3‐Amino‐2,4,5,7‐tetrahydro‐6 H ‐pyrazolo[3,4‐ b ]pyridin‐6‐ones

• Published in: ChemistrySelect (Weinheim) 2017-05, Vol.2 (13), p.3668-3672
• Main Authors: Bou‐Petit, Elisabeth, Picas, Elsa, Puigjaner, Cristina, Font‐Bardia, Mercè, Ferrer, Nabí, Sempere, Julià, Puig de la Bellacasa, Raimon, Batllori, Xavier, Teixidó, Jordi, Estrada‐Tejedor, Roger, Ramon y Cajal, Santiago, Borrell, José I.
• Format: Article
• Language: English
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201700732

The reaction between pyridones ( 1 ) and substituted hydrazines 4 can afford two different regioisomeric pyrazolo[3,4‐ b ]pyridin‐6‐ones 2 and 3 depending on the initial substitution of the methoxy group and the direction of the cyclization. In the case of phenylhydrazine 4 (R 3 = Ph), we have clearly shown that the treatment of pyridones 1a–d with 4 (R 3 = Ph) in MeOH at temperatures below 140°C yields, independently of the nature and position of the substituents present in the pyridone ring, the open intermediates 7a–d . When the reaction is carried at 140°C under microwave irradiation, the corresponding 2‐aryl substituted pyrazolo[3,4‐ b ]pyridines 3a–d are always formed. We have experimentally determined, using DSC techniques, the activation energies of the two steps involved in the formation of 3 : a) substitution of the methoxy group present in pyridones 1 with phenylhydrazine 4 (R 3 = Ph) to afford intermediates 7 and b) cyclization of intermediates 7 to yield pyrazolopyridines 3 . The results obtained, 15 and 42 kcal⋅mol −1 respectively, are in agreement with the experimental findings.