A general synthesis of arylindoles and (1-arylvinyl)carbazoles via a one-pot reaction from N-tosylhydrazones and 2-nitro-haloarenes and their potential application to colon cancer

Abstract

A convergent and effective synthesis of 3-aryl-indoles, 2,3-diaryl indoles, and (1-arylvinyl)carbazoles from a one-pot sequence involving the coupling of N-tosylhydrazones with ortho-nitro-haloarenes followed by a cyclization has been developed. Compound 5i exhibits excellent antiproliferative activity in the low nM range against colon cancer cell lines.

Pyrrolo-imidazo[1,2-a]pyridine Scaffolds through a Sequential Coupling of N-Tosylhydrazones with Imidazopyridines and Reductive Cadogan Annulation, Synthetic Scope, and Application

“…Yellow solid (108 mg, 62% yield); mp 175-177 ºC; Rf = 0.3 (cyclohexane/ethyl acetate 8/2); IR (film, cm -1 ): 1724, 1520, 1371, 1354, 1289, 1272, 1203, 1156, 1106, 759, 6,117.8,117.6,117.5,110.6,85.0,28.3 (3CH3), 21.5 (CH3). HRMS (ESI): for C21H22N3O2 (M + H) + : m/z calcd.…”

“…-pyrrolo[3',2':4,5]imidazo [1,2-a]pyridine- 1-carboxylate (5j). Yellow solid (128 mg, 49% yield); 181-183 ºC; Rf = 0.3 (cyclohexane/ethyl acetate 8/2); IR (film, cm -1 ): 1728, 1519, 1505, 1372, 1354, 1156, 1109, 1061, 838, 759, 6,147.6,138.2,133.5,128.9,128.0 (d,J = 7.8 Hz,2CH),126.3,123.8,118.4,117.9,116.8,115.8 (d,J = 21.6 Hz,2CH),110.7,85.3,28.3 (3CH3); mixture was subjected to microwave irradiation with stirring at 100 °C for 30 minutes. After the system had cooled down to room temperature, the reaction was diluted with H2O, and extracted with ethyl acetate.…”

“…1). 6 Encouraged by these results, we planned to develop a new synthesis which permits us the generation of new scaffolds of biological interests. Imidazo [1,2-a]pyridines is an important biologically active moiety, with a growing interest in medicinal chemistry.…”

C‐N and N‐N bond formation via Reductive Cyclization: Progress in Cadogan /Cadogan‐Sundberg Reactionǂ

“…A variety of (1‐arylvinyl) carbazoles were obtained from N ‐tosylhydrazones and 2‐nitro‐haloarenes using PPh 3 as reducing agent in dioxane for cyclization. The carbazoles were evaluated for anti‐proliferative activity and the results showed 71 to be the most potent anti‐proliferative agent with IC 50 = 2.3 nM against colon cancer cell lines (Scheme ). In 2017, an aryl‐substituted carbazole‐based solvatochromic bluish fluorophore 73 was synthesized via one pot Suzuki cross‐coupling and Cadogan cyclization (Scheme ).…”

Pyridylmethylamine–Palladium Catalytic Systems: A Selective Alternative in the C−H Arylation of Indole

“…Considerable efforts have been directed towards the development of efficient methodst oi nstall aryl groups selectively at the indole nucleus. Aryl indoles can be prepared through construction of the indole core (e.g.,F ischeri ndole synthesis), [1] through traditional coupling reactions requiring the preparation of prefunctionalized substrates (e.g.,b oronatesa nd halides), [2] and also throughC ÀHa rylation of unsubstitutedi ndoles. [3] In this context, the selective CÀHa rylation of indole is an especially challenging transformation, for which the triptychl igand-metalbase is crucial.…”