Site-Selective Suzuki–Miyaura Reaction of 6,8-Dichloro-1,2,4-triazolo[4,3-a]pyridines

Abstract

Triazolopyridines have found various applications as pharmaceuticals, agrochemicals, or optical materials. Consequently, the introduction of various functionalities at specific sites of this heterocyclic framework is of great importance. In this regard, we report the development of a site-selective Suzuki–Miyaura reactions leading to substituted triazolopyridines at positions 6 and 8. Under optimized conditions, the respective products have been obtained with high selectivity and yield.

Key words

triazolopyridines - regioselectivity - aryl chlorides - palladium catalysis - Suzuki–Miyaura reaction

• References and Notes

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• 10a Triazolopyridines 3a–m; General Procedure Triazolopyridine 1 or 2 (0.57 mmol, 150 mg), the appropriate boronic acid (1.31 mmol, 2.3 equiv), K₃PO₄ (2.27 mmol, 482 mg, 4.0 equiv), Pd(OAc)₂ (0.03 mmol, 6.3 mg, 5 mol%), and SPhos ligand (0.06 mmol, 23.0 mg, 10 mol%) were added to an argon-flushed glass pressure tube. Toluene (5 mL) was added, and the mixture was heated to 100 °C for 24 h, then cooled. The solvent was evaporated, and the crude product was purified by column chromatography (silica gel, heptane–EtOAc). 3,6,8-Triphenyl[1,2,4]triazolo[4,3-a]pyridine (3a) White solid; yield: 189 mg (96%); mp 206–207 °C. IR (ATR): 3367 (w), 3075 (w), 2965 (w), 2922 (w), 2864 (w), 1478 (m), 1446 (w), 1359 (w), 1265 (w), 1076 (w), 888 (w), 839 (w), 764 (s), 695 (s), 591 (m), 512 (m), 449 (w) cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.36 (d, J = 1.5 Hz, 1 H), 8.23–8.16 (m, 2 H), 7.93–7.86 (m, 2 H), 7.70 (d, J = 1.5 Hz, 1 H), 7.66–7.41 (m, 11 H). ¹³C NMR (75 MHz, CDCl₃): δ = 118.22 (CH), 126.23 (CH), 126.84 (C), 127.29 (2 CH), 128.73, 128.92, 129.03, 129.39 (CH), 129.41, 129.47, 129.53, 129.91, 130.45 (CH), 134.84, 136.61, 147.59, 149.11. MS (EI): m/z (%) = 347 [M ⁺ ] (100), 244 (20), 216 (18), 189 (12), 165 (3), 140 (4), 103 (7), 77 (5). HRMS (EI): m/z [M]⁺ calcd for C₂₄H₁₇N₃: 347.14170; found: 347.14106.