Palladium‐Catalyzed Coupling of Aldehyde‐Derived Hydrazones: Practical Synthesis of Triazolopyridines and Related Heterocycles

Abstract

The palladium‐catalyzed intermolecular coupling of aldehyde‐derived hydrazones with chloroazines, followed by oxidative cyclization under mild conditions afforded access to a broad variety of bicyclic heterocyclic scaffolds (see scheme) that have potential for use in drug discovery.

Design, Synthesis and Characterisation of Novel Phenothiazine‐Based Triazolopyridine Derivatives: Evaluation of Anti‐Breast Cancer Activity on Human Breast Carcinoma

“…Target compounds 8 a‐e were finally synthesized by the oxidative cyclisation of respective phenothiazine pyridylhydrazones 7 a ‐ e as depicted in Scheme . Various reagents like chloramine‐T, NBS/DBU and I 2 /K 2 CO 3 were scrutinized for this transformation. Very low yields were obtained with chloramine‐T for the oxidative cyclisation while several impurities or by products were observed with NBS/DBU.…”

Synthesis of 1,2,4‐Triazolo[4,3‐a]pyridines and Related Heterocycles by Sequential Condensation and Iodine‐Mediated Oxidative Cyclization

“…Compound 1 a : Yield: 94 mg, ≥ 95 % (0.5 mmol scale); 1.15 g, ≥ 95 % (6 mmol scale); off‐white solid, m.p. 171–173 °C (lit . m.p.…”

“…Compound 1 j : Yield: 108 mg, 90 %; brown solid; m.p. >300 °C; R f =0.4 (MeOH/CH 2 Cl 2 2:98); 1 H NMR (400 MHz, CF 3 CO 2 D): δ =8.98 (d, J =6.8 Hz, 1 H), 8.84–8.81 (m, 2 H), 8.50–8.38 (m, 4 H), 7.91 ppm (td, J =7.2, 0.8 Hz, 1 H); 13 C NMR (100 MHz, CF 3 CO 2 D): δ =150.1, 145.5, 145.0, 139.0, 130.3, 128.1, 124.9, 119.9, 111.3 ppm; HRMS: m / z calcd for C 12 H 9 N 4 O 2 [ M +H] + : 241.0720; found: 241.0722.…”

“…A survey of the literature indicated that 1,2,4‐triazolo[4,3‐ a ]pyridines could be prepared by the following strategies (Scheme ): a) cyclodehydration of acylated 2‐hydrazinopyridines in acetic acid under microwave irradiation or by using Lawesson's reagent; b) tandem/one‐pot reaction of 2‐hydrazinopyridines with carboxylic acids in the presence of reagents such as POCl 3 /PCl 5 , polystyrene‐bound triphenylphosphine (PS‐PPh 3 )/CCl 3 CN, and 1,1′‐carbonyldiimidazole (CDI); with isothiocyanates promoted by polymer‐supported Mukaiyama's reagent; or with aryl iodides through [Mo(CO) 6 ]‐mediated carbonylation; c) oxidative cyclization of 2‐pyridylhydrazones with oxidants such as hypervalent iodine reagents, N ‐bromosuccinimide (NBS), chloramine T, ceric ammonium nitrate (CAN), and CuCl 2 ; and d) Cu‐catalyzed direct C−H (hetero)arylation of preformed 1,2,4‐triazolo[4,3‐ a ]pyridines …”

Pd-Catalyzed Ag(I)-Promoted C3-Arylation of Pyrido[1,2-a]pyrimidin-4-ones with Bromo/Iodo-Arenes

“…21 In approach of Suzukicoupling reaction 22 of C3-bromo/chloro derivatives of pyridopyrimidinones with arene boronic acids, the hydrodehalogenation reaction was found to compete in significant extent. In addition, direct arylations have been documented for pharmaceutically-important numerous N-fused heterocyclic motifs, for example, imidazo[1,2-a]pyridines, 31 indolizines, 32 pyrazolo[1,5a] [1,3,5]triazin-4(3H)-ones, 33 imidazo[1,2-a]pyrazines 34 and imidazo[1,2-b]pyridazines. 35 These structural aryl-modulation of N-fused bicycles have been found useful in the discovery of new potent bioactive agents.…”