Heterocyclic o-Aminonitriles: Preparation of Pyrazolo[3,4-d]-pyrimidines with Modification of the Substituents at the 1- Position

Abstract

Novel 1-[6-(p-tolyl) pyridazin-3-yl]pyrazole-o-aminonitriles (3a-c) were formed using 3-hydrazino-6-(p-tolyl)pyridazine (2) and ketene S,S-acetals (1a), S,N-acetals (1b) or tetracyanoethylene (1c). The pyrazole-o-aminonitriles (3a-c) were in turn used as precursors for the preparation of previously unreported 1-[6-(p-tolyl)-pyridazin-3-yl]pyrazolo[3,4-d]pyrimidines (8, 9, 13-20) and 7-[6-( p-tolyl) pyridazin-3-yl]2-arylpyrazolo[3,4-d]1,2,4-triazolo[5,1-f]pyrimidines (10-12) which are expected to possess considerable chemical and pharmacological activities.

4‐Arylation of N‐Acylamino‐ and Aminopyrazoles by the Suzuki–Miyaura Cross‐Coupling Reaction

“…The amount of base was found to be critical. One equivalent of K 2 CO 3 led to the incomplete consumption of the starting material, whereas 3 or 4 equivalents of K 2 CO 3 led to an increase in the rate of hydrodehalogenation (entries [15][16][17]. Comparison of different solvent systems (entries [18][19][20] revealed a mixture of dioxane and water to be optimal for the reaction.…”

Reactions of Substituted Carbohydrazides with Electron-poor Olefins

“…One-pot reactions between carboxylic hydrazides and 2-isothiocyanatobenzonitrile afford pharmacologically relevant 1,2,4-triazolo [1,5-c]quinazoline-5-thiones [2]. Hydrazide compounds can also be converted to triazole-3-thiols [3], 1,3,4-oxadiazole [4], 1,3,4-oxadiazine [4], pyrazolotriazolopyrimidine [5,6] and pyrazolotriazoloquinoline derivatives [7]. 1,2,4-Triazines are formed via the condensation of 1,2-diketones with acylhydrazides and ammonium acetate under traditional thermal and dry media microwave-assisted reaction conditions [8,9].…”

Synthesis, reactions, and antimicrobial activity of some novel pyrazolo[3,4‐d]pyrimidine, pyrazolo[4,3‐e][1,2,4]triazolo[1,5‐c]pyrimidine, and pyrazolo[4,3‐e][1,2,4]triazolo[3,4‐c]pyrimidine derivatives

“…[4] Reports from our laboratory [5] and from others [6] revealed that the possible route for the synthesis of pyrazolo [4,3-e] [1,2,4]triazolo [1,5-c] pyrimidine derivatives involves reaction of 5-amino-4-imino-pyrazolo [3,4-d]pyrimidine with one-carbon cyclizing agents. Furthermore, attempts to prepare the isomeric pyrazol [4,3-e] [1,2,4]triazolo [4,3-c] pyrimidines via dehydrative cyclization of the 4-acylhydrazinopyrazolo [3,4-d]pyrimidines were reported to give the corresponding pyrazolo [4,3-e] [1,2,4]triazolo [1,5-c]pyrimidines. [7] In the light of these findings and in continuation of our ongoing research work on the chemistry of hydrazonoyl halides, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] it was thought interesting to synthesize new series of pyrazolo [3,4-d]pyrimidine and pyrazolo [4,3-e] [1,2,4]triazolo [3,4-c]pyrimidine derivatives.…”

“…Our interest in developing a new synthsis of these two ring systems results from the fact that some derivatives of both pyrazolo [3,4-d] [1,2,4]triazolo [1,5-c]pyrimidine and pyrazolo [4,3-e] [1,2,4]triazolo [3,4-c]pyrimidine derivatives exhibit interesting pharmacological activities [24] ; for example, several 3-and/or 5-substituted 7H-pyrazolo [4,3-e] [1,2,4]triazolo [3,4-c]pyrimidines were reported to be potent xantheine oxidase (XO) inhibitors. [24] Also, pyrazolo [3,4-d] [1,2,4]triazolo [1,5-c]pyrimidine is one of the structural requirements for compounds that have as selective antagonists for human A 2A and A 3 adenosine receptor subtypes.…”

“…Oxidation of each of the compounds 19-21 with ferric chloride in ethanol resulted in the formation of the corresponding 1,3,6-triarylpyrazolo [3,4-d] [1,2,4] triazolo [3,4-e]pyrimidines 22-24 (Scheme 3). The formation of compounds 22-24 is assumed to be via oxidation of compounds 18-21 that affords the corresponding nitrilimines followed by in situ 1,5-electrocyclization.…”