N-{4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-5-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide → N-{4-[4-(4-Chlorobenzyl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-5-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-{4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-5-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide (0.292 g, 0.589 mmol) in tetrahydrofuran (4.1 mL) was added 4-chlorobenzylzinc chloride (0.50M solution in tetrahydrofuran, 2.36 mL, 1.18 mmol) and bis(tri-t-butylphosphine)palladium(0) (0.0226 g, 0.0442 mmol) under argon. The solution was stirred at 60° C. for 2 hours. The reaction was incomplete by LCMS, so additional 4-chlorobenzylzinc chloride (0.50M solution in tetrahydrofuran, 2 mL, 1 mmole) was added, then the reaction was stirred at 60° C. for an additional 2 hours. The reaction was allowed to cool to room temperature then the solvent was evaporated in vacuo. Column chromatography was performed to yield the title compound (0.112 g, 35%). LCMS: (FA) ES+, 542. 1H NMR (400 MHz, d4-methanol) δ: 8.73-8.69 (m, 1H), 8.42-8.38 (m, 1H), 8.14 (s, 1H), 7.58-7.55 (m, 1H), 7.27-7.20 (m, 4H), 5.52 (s, 2H), 4.32 (s, 2H), 3.68-3.61 (m, 2H), 2.20 (s, 3H), 0.90-0.84 (m, 2H), 0.040 (s, 9H).

Provenance & Evidence