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

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-2-methylpyrazolo[1,5-a]pyridine (0.200 g, 0.407 mmol) in tetrahydrofuran (2.8 mL) were added 4-chlorobenzylzinc chloride (0.50M solution in tetrahydrofuran, 1.63 mL, 0.814 mmol) and bis(tri-t-butylphosphine)palladium(0) (0.0156 g, 0.0305 mmol) under argon. The solution was stirred at 60° C. for 3 hours. The reaction was incomplete by LCMS, so additional 4-chlorobenzylzinc chloride (0.50M solution in tetrahydrofuran, 1.0 mL, 0.5 mmole) was added then the reaction was stirred at 60° C. for an additional 3 hours. The reaction was cooled to room temperature then the solvent was evaporated in vacuo. The residue was purified by column chromatography (SiO2, elution with EtOAc in hexanes 10-100% gradient) to yield the title compound (0.188 g, 86%). LCMS: (FA) ES+ , 538. 1H NMR (400 MHz, d6-DMSO) δ: 8.87 (s, 1H), 8.76-8.72 (m, 1H), 8.28-8.24 (m, 1H), 7.54-7.48 (m, 1H), 7.44-7.40 (m, 2H), 7.35-7.30 (m, 2H), 7.09-7.03 (m, 1H), 5.58 (s, 2H), 4.63 (s, 2H), 3.68-3.62 (m, 2H), 2.66 (s, 3H), 0.91-0.84 (m, 2H), 0.050 (s, 9H).

Provenance & Evidence