Benzotriazole-Assisted Preparations of 2-(Substituted amino)pyridines and Pyrid-2-ones

Abstract

Base-promoted reactions of benzotriazolyl-containing acetic acid derivatives, 2-(benzotriazol-1-yl)acetonitrile (7a), 2-(benzotriazol-1-yl)acetamide (7b), and (±)-2-(benzotriazol-1-yl)propionamide (7c), with α,β-unsaturated ketones 8 give efficient and regioselective access to previously difficult to attain 3-unsubstituted pyridine derivatives: the 2-(substituted amino)pyridines 14a−k and the 4,6-substituted pyrid-2-ones 15a−h. The pyridine rings result from tandem [3 + 3] annulations involving a Michael addition followed by cyclization.

Modification of the Structure of 4, 6‐Disubstituted 2‐(4‐Alkyl‐1‐piperazinyl)pyridines: Synthesis and Their 5‐HT2A Receptor Activity

“…To synthesize the new compounds 6-17, we applied the benzotriazole-assisted Katritzky method [14] for the reaction of α,β-unsaturated ketones with 2-(1-benzotriazolyl)acetonitrile and sec-amines such as diethylamine, piperidine, pyrrolidine, or morpholine in ethanol; after a 48-hour reflux, they afforded the corresponding 4,6-disubstituted 2-(substituted amino)pyridines. In our study we used N-methyl-or N-benzylpiperazine as a sec-amine substrate.The starting α,β-unsaturated ketones were synthesized by a classical chalcone method, in the reaction of the appropriate aldehyde and acetophenone derivative in ethanol-aqueous NaOH medium at the room temperature.…”

“…Equimolar amounts (3 mmol) of 2-(1-benzotriazolyl)acetonitrile [14] and appropriate α,β-unsaturated ketone with Nmethylpiperazine (2 mL) were refluxed in EtOH (10 mL) for 48 h. The solvent was evaporated, and the residue was dissolved in CHCl 3 (20 mL), washed with 10 % NaOH then with brine, and dried over anhydrous MgSO 4 . After evaporation of the solvent the residue was purified by column chromatography as follows: 6, 9, and 12-14 -SiO 2 …”

An efficient microwave‐assisted synthesis of 3,5‐unsubstituted 4‐substituted‐6‐aryl‐3,4‐dihydropyridin‐2(1H)‐ones derivatives

“…Numerous methods for the preparation of the 4,6-diaryl-2-pyridone template have been reported many times in the literature, such as the synthesis of 3-substituted-2-pyridone [6][7][8] derivatives (A) which are functionalized at the 3 and 4 position. In addition, slight modification of the 4,6-diaryl-2-pyridone nucleus was reported to afford a series of 3-unsubstituted 2-pyridone derivatives [5,[9][10][11] (B) which provide new series of biologically active compounds.…”

Preparation of 2-Pyridone-Containing Tricyclic Alkaloid Derivatives as Potential Inhibitors of Tumor Cell Proliferation by Regioselective Intramolecular N- and C-Acylation of 2-Pyridone

“…[35][36][37] By scanning the conditions, the best yield (63%) of desired 2-pyridone 8a was obtained when chalcone 7a was refluxed with 2-(benzotriazol-1-yl)acetamide 35) in the presence of NaOH for 6 h. Under similar conditions, other compounds 7b-j were annulated to give the corresponding products 8b-j in 60-75% yields. It is worthy to note that the heterocycles 8i-j showed good toleration of the conditions (Table 2).…”

“…Among the methods for preparation of 3-unsubstituted 2-pyridone, [27][28][29][30][31][32][33][34][35][36][37] [3ϩ3] annulation between chalcone and C-C-N fragment connected with a leaving group displayed high convenience and efficiency, such as N-(2-carbamoylmethyl)-pyridinium ylide, [29][30][31][32][33] 2-acetamidoacetamide 34) or 2-(benzotriazol-1-yl)acetamide. [35][36][37] By scanning the conditions, the best yield (63%) of desired 2-pyridone 8a was obtained when chalcone 7a was refluxed with 2-(benzotriazol-1-yl)acetamide 35) in the presence of NaOH for 6 h. Under similar conditions, other compounds 7b-j were annulated to give the corresponding products 8b-j in 60-75% yields.…”