Unexpected Hydrazinolysis Behaviour of 1-Chloro-4-methyl-5H-pyridazino[4,5-b]indole and a Convenient Synthesis of New [1,2,4]-Triazolo[4’,3’:1,6]pyridazino[4,5-b]indoles

Abstract

Abstract:Reaction of the title compound with hydrazine in the presence of air gives the 1-unsubstituted parent system via oxidative dehydrazination of the 1-hydrazino intermediate. The latter can be obtained in high yield by carrying out the hydrazinolysis step under inert gas, and it is smoothly converted into [1,2,4]-triazolo[4',3':1,6]pyridazino [4,5-b]indoles.

Synthesis and functionalization of some new pyridazino[4,5-b]indole derivatives

“…This behaviour is not surprising, as we had previously observed an analogous transformation with a similar pyridazinoindole. 15,16 The 1-unsubstituted pyridazine 24 could be prepared alternatively by catalytic transfer hydrogenation of 19 using ammonium formate as the hydrogen source and Pd/C as a catalyst in refluxing methanol, affording analytically pure 24 in 68% yield. In agreement with the proposed structure, the 1 H-NMR spectrum showed a new singlet at 9.68 ppm which is assigned to the pyridazine proton (H-1), thus proving the successful removal of the chloro substituent.…”

“…14 During the past few years, we have investigated the synthesis and biological activity of various new representatives of this "aza-carboline" ring system, mainly focusing on potential antitumor agents. [15][16][17] Encouraged by the pharmaceutical importance of these ring systems, we decided to…”

Concise syntheses of 5-substituted pyridazino[4,5-b]indolones and -diones

“…23,24 The final hydrolysis step, affording the new pyridazinone 10, succeeded by heating the chloropyridazine in acetic acid. 25 As a more convenient synthesis of 10, which moreover avoids the use of toxic mercuric oxide, we elaborated a sequence starting from N-propylindole-2-carboxylic acid ethyl ester 26 (11). This compound could be easily formylated at C-3 with Vilsmeier-Haack reagent under the conditions reported for similar substrates.…”

“…[1][2][3][4][5][6][7][8][9] During the past few years, we have investigated the synthesis and biological activity of various new representatives of this "aza-carboline" ring system, mainly focusing on potential antitumor agents. [10][11][12] The title ring system now became interesting also in the context of an ongoing program in search of new and selective inhibitors of copper-containing amine oxidases. 13 Based on preliminary structure-activity information, 14 the need arose to prepare a focused compound library of indole-fused pyridazinones and pyridazinediones bearing various alkyl substituents at the indole nitrogen.…”

Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles

“…Given the intriguing structures and the medicinal importance of polycyclic indole-based molecules [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ], we envisioned that the amalgamation of the indole moiety [ 8 , 9 , 10 , 11 , 12 , 13 ] with the pyridazine ring [ 14 , 15 , 16 , 17 , 18 , 19 ] that potentially generates different isomeric scaffolds ( a – c ) would lead to entities endowed with either amplified or new biological activities ( Figure 1 ). A large number of reports dedicated to the synthesis of these appealing frameworks and studies on their pharmacologic activities appeared in the literature in the past few decades [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Among the heterocyclic architectures a – c , the tricyclic fused indole-pyridazine system c which can be considered to be aza-analogous (or bioisoster) of β-carboline, the unique tricyclic pyrido[3,4- b ]indole core amenable to an important family of bioactive natural products widely distributed in nature [ 30 ], has attracted our attention.…”