Improved and expanded one-pot, two-component Boulton-Katritzky syntheses of N–N bond containing bicyclic heterocycles

Access and modulation of substituted 1-methyl-1,6-dihydropyrazolo[3,4-c]pyrazoles

“…In summary, the quick access towards variously functionalized pyrazolo[3,4-c]pyrazoles is herein described, starting from 5bromo-1-methyl-1H-pyrazole-4-carbaldehyde (1). The approach relies on the use of substituted aromatic hydrazines engaged in efficient one-pot sequences.…”

“…The most prominent include biological macromolecules (DNA and RNA with their purine bases), proteins and peptides, as well as physiologically important biomolecules (serotonin, melatonin etc.). 1 In contrast, bicyclic heterocycles containing a nitrogennitrogen (N-N) bond are relatively rare in nature, but nonetheless prevalent in the pharmaceutical industry. 2 Such a class is well represented by the ring-contracted [5:5] bicyclic aromatic rings.…”

“…8 The synthesis of this bicyclic scaffold are scarcely found in the literature and are almost exclusively based on an existing pyrazole motif. [9][10][11] The desired bicyclic framework is aerward obtained either according to a mononuclear heterocyclic rearrangement 1,8 (known as Boulton-Katritzky rearrangement -Route A), an annulation strategy (Route B) [12][13][14][15][16][17] or other miscellaneous methods (using isothiocyanates, 18 nitrilimines, 9 arylsemicarbazides 19 or 2-cyano-N-methyl-acrylamide 20 ).…”

One-pot synthesis of functionalized pyrazolo[3,4-c]pyrazoles by reaction of 2-cyano-N-methyl-acrylamide, aryl aldehyde, and hydrazine hydrate

“…Pyrazoles are relatively rare in the nature but can be found widely in the pharmaceutical and biochemical industries. 1,2 Also, monocyclic pyrazoles are useful scaffolds for the synthesis of larger fused heterocyclic systems. Among them, we can mention pyrazolo-fused pyrimidines, 3 quinolines, 4 pyridines, 5 thiazoles, 6 isoquinolines, 7 imidazoles, 8 diazepines, 9 and triazines.…”

“…10 Fused pyrazoles are important classes of heterocycles with effective biological activity such as antitumor, 11 antioxidant, 2 antimicrobial, 12 antiviral, 13 and as immunostimulatory agents. 14 Moreover, some of these bicyclic heterocycles are used for treatment of autoimmune/inflammatory diseases, 1 useful for treatment of esophageal and gastrointestinal mucosa injury, 14 and potent inhibitors of hGSK-3a. 15 Among the fused pyrazoles are pyrazolo [3,4-c]pyrazoles, which are important owing to their various pharmacological and biological activities such as adenosine mimics (A), 16 antibiotics (B), 17 and anticancer (C), 18 which have inhibitory activity against liver cancer (HepG2) Cell Category (D) 19 (Figure 1).…”