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An Unequivocal Synthesis of 2‐Aryl Substituted 3‐Amino‐2,4,5,7‐tetrahydro‐6 H ‐pyrazolo[3,4‐ b ]pyridin‐6‐ones
Author(s) -
BouPetit Elisabeth,
Picas Elsa,
Puigjaner Cristina,
FontBardia Mercè,
Ferrer Nabí,
Sempere Julià,
Puig de la Bellacasa Raimon,
Batllori Xavier,
Teixidó Jordi,
EstradaTejedor Roger,
Ramon y Cajal Santiago,
Borrell José I.
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201700732
Subject(s) - phenylhydrazine , chemistry , yield (engineering) , ring (chemistry) , aryl , medicinal chemistry , stereochemistry , organic chemistry , alkyl , materials science , metallurgy
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.