Potassium Carbonate → 3-[4-Bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-5-(diethoxymethyl)-2-methylpyrazolo[1,5-a]pyridine

Participants

Reaction Steps

To a mixture of 3-(4-bromo-2-prop-1-yn-1-yl-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole [Prepared as described in Example 14 (4.37 g, 10.9 mmol)] and potassium carbonate (3.00 g, 21.7 mmol) in dry N,N-dimethylformamide (20.0 mL) was added a solution of 1-amino-4-(diethoxymethyl)pyridinium 2,4,6-trimethylbenzenesulfonate (6.37 g, 15.6 mmol) in dry N,N-dimethylformamide (20.0 mL) over 10 min. The resulting dark brown solution was stirred at rt for 40 hours. The mixture was added to ˜250 mL of ice water with stirring, then was extracted with EtOAc (100 mL×5) until the aqueous layer turned into a clear solution. The combined EtOAc extracts were washed with water, brine, dried over Na2SO4, filtered, and evaporated. The crude product was purified by column chromatography on silica gel, using EtOAc/hexane (0/100 to 50/50) as an eluant to give a solid product (4.56 g, 70.2%). LCMS: (FA) ES+ 593, 595. 1H NMR (400 MHz, CDCl3) δ: 8.46 (d, J=2.01 Hz, 1H), 8.40-8.42 (d, J=7.28 Hz, 1H), 8.32 (s, 2H), 7.05-7.08 (dd, J=2.01, 7.03 Hz, 1H), 5.57 (s, 2H, 3.68-3.77 (m, 4H), 3.58-3.63 (m, 2H), 2.75 (s, 3H), 1.28-1.32 (m, 6H), 0.95-1.00 (m, 2H), 0.02 (s, 9H)

Provenance & Evidence