Synthesis of 5-Aryl-5H-pyrido[2',1':2,3]imidazo[4,5-b]indoles by Domino Pd- and Cu-Catalyzed C–N Coupling Reactions

Abstract

A series of 5-aryl-5H-pyrido[2',1':2,3]imidazo[4,5-b]indoles was successfully prepared in good yields by a practical four-step strategy. In this procedure, the key step was demonstrated to be the domino Pd-and Cu-catalyzed C–N coupling reactions of 3-bromo-2-(2-bromophenyl)imidazo[1,2-a]pyridine with amines.

Key words

fused N-heterocycles - C–N coupling - Pd catalysis - Ullmann reaction - domino reaction

• References and Notes

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• 31 Typical Procedure: Preparation of 5-Phenyl-5H-pyrido[2',1':2,3]imidazo[4,5-b]indole (9a) Aniline (40 mg, 0.426 mmol, 1.5 equiv) was added to a pressure tube that was charged with 7 (100 mg, 284 μmol, 1 equiv), Pd₂(dba)₃ (13 mg, 14 μmol, 0.05 equiv), Xantphos (16 mg, 28 μmol, 0.1 equiv), CuI (5 mg, 28 μmol, 0.1 equiv) and sodium tert-butoxide (164 mg, 1.7 mmol, 6 equiv) under argon. The tube was back-flushed with argon several times. Then, degassed anhydrous toluene (5 mL) was added under argon. The reaction mixture was heated at 110 °C for 12 h. After cooling, the reaction mixture was diluted with dichloromethane (20 mL), and the resulting mixture was filtered through a pad of Celite^®, which was washed with dichloromethane (3 x 40 mL). The filtrate was concentrated in vacuo. The crude product was purified by flash chromatography (silica gel; hexane/dichloromethane/ ethyl acetate, 8:1:1) to yield 9a (50 mg, 62%) as a yellowish solid. Mp 168–170 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.18–8.13 (m, 1 H), 7.77–7.70 (m, 2 H), 7.68–7.61 (m, 2 H), 7.58–7.55 (m, 1 H), 7.55–7.47 (m, 3 H), 7.33 (dd, J = 6.1, 3.1 Hz, 2 H), 7.11 (ddd, J = 9.3, 6.7, 1.4 Hz, 1 H), 6.70 (td, J = 6.7, 1.2 Hz, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 144.62, 141.03, 135.68, 131.37, 129.02, 128.38, 126.80, 125.53, 122.90, 121.40, 120.90, 120.13, 118.72, 117.89, 117.49, 109.90, 109.78. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₁₃N₃: 284.1188; found: 284.1190.