Synthesis of new pyrazolo[3,4-b]pyridines and related fused tricyclic systems with possible biological activities

Article history : Received: 2/6/2014 ; Revised : 26/6/2014 ; Accepted : 29/6/2014 ; Available Online : 1/6/2015; Abstract The reaction of 5-acetyl-3-cyano-4-(p-methoxyphenyl)-6-methylpyridine-2(1H)-thione (1) with methyl iodide gave 2-methylthio derivative 2. Heating of 2 with hydrazine hydrate produced the target 5-acetyl-3-amino-4-(p-methoxyphenyl)-6methylpyrazolo[3,4-b]pyridine (3). Reaction of 3 with some reagents, namely acetylacetone, ethyl acetoacetate, diethyl malonate and ethyl α-cyano-β-ethoxyacrylate were carried out and their products were identified. Diazotisation of aminopyrazole 3 gave the isolable diazonium salt, 5-acetyl-4-(p-methoxyphenyl)-6-methylpyrazolo [3,4-b]pyridine-3-diazonium chloride (10). The reactivity of 10 was checked by coupling with β-naphthol whereby the azo dye 11 was isolated. Also, coupling of 10 with active methylenes such as: barbituric acid, 3-methyl-1-phenyl-2-pyrazolin-5-one, 1,3-diphenyl-2-pyrazolin-5-one, malononitrile, ethyl cyanoacetate, cyanothioacetamide and/ or phenacylcyanide furnished the corresponding hydrazono compounds 12, 13a,b and 14a-d. Cyclization of 14a-d into the corresponding 4-aminopyridopyrazolotriazines 15a-d was achieved in boiling acetic acid. In contrast, reaction of 10 with acetyacetone or ethyl benzoylacetate furnished pyridopyrazolotriazines 17a and 17b directly.