Site-selectivity in hydrazinolysis of 3,4'-bis-(functionalized carbonyl)-4,3'-bis(pyrazolyl)ketones. A convenient synthesis of 4-(pyrazol-3-yl)-2H-pyrazolo[3,4-d]-pyridazines

Abstract

Reaction of hydrazine hydrate with 3,4-bis-(functionalized carbonyl)-4,3-bis(pyrazolyl)ketones proceeds regioselectively affording the corresponding 4-(pyrazol-3-yl)-2H-pyrazolo [3,4-d]pyridazine derivatives in high yields. The structures of the products were determined by spectroscopic and elemental analyses and supported by comparison with the possible isomers prepared by an independent route.

Serendipitous Formation of 2H-Pyrazolo[3,4-d]pyridazin-7(6H)-ones from 3-Arylsydnones

“…The yield of the product was also increased up to 94%. This report for pyrazolopyridazin-7-one analogues 7a–l is more advantageous than other reported methods − as the synthetic method includes the shorter reaction time, easy workup, and excellent yields by using DMF/POCl 3 as a solvent. The proposed mechanism of conversion of hydrazone of 4-acetyl-3-arylsydnones 4a–l to pyrazolo­[3,4- d ]­pyridazin-7­(6 H )-ones 7a–l is presented in Scheme .…”

“…A useful method for the preparation of pyrazole and pyrazolopyridazine derivatives is the nucleophilic addition of hydrazines to 4-acyl-furandiones in boiling benzene . Pyrazolopyridazine/ones have been obtained by various methods, that is, (i) pyrazole-3-carboxylic acid with 2,5-dichlorophenylhydrazine ( 4 ), (ii) 1-phenyl-4-(2-thienylcarbonyl)-pyrazole-3-carboxylate ( 5 ), and (iii) 4-benzoyl-5-phenyl-2,3-dihydro-2,3-furandione ( 6 ) (Scheme ). Three position isomers have been reported by different methods of synthesis such as pyrazolo­[1,2- a ]­pyridazine-5,8-diones, pyrazolo­[3,4- d ]­pyridazinones, and pyrazolo­[4,3- c ]­pyridazines .…”

“…A useful method for the preparation of pyrazole and pyrazolopyridazine derivatives is the nucleophilic addition of hydrazines to 4-acyl-furandiones in boiling benzene. 31 Pyrazolopyridazine/ones have been obtained by various methods, that is, (i) pyrazole-3-carboxylic acid with 2,5-dichlorophenylhydrazine (4), 32 (ii) 1-phenyl-4-(2-thienylcarbonyl)-pyrazole-3-carboxylate (5), 33 and (iii) 4benzoyl-5-phenyl-2,3-dihydro-2,3-furandione ( 6) 34 Several derivatives of pyrazolopyridazines exhibit potential activities such as antifungal, 36 antibacterial, 37 anti-inflammatory, analgesic, antihypoxic, antipyretic agents, 38 and antimicrobial actions. 39 Also, some pyrazolopyridazine derivatives are reported to be inhibitors of cyclin-dependent kinase 1 (CDK1), 40 phosphodiesterase 4 (PDE4) inhibitors, which are widely used in therapeutic treatment of inflammatory and immune disorders, 41 including glycogen synthase kinase 3 (GSK-3) inhibitors.…”