(Trifluoromethyl)trimethylsilane → N-(5-(5-(3-hydroxy-3-(trifluoromethyl)cyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Participants

Reaction Steps

To a stirring solution of N-(2-methyl-5-(5-(3-oxocyclobutyl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (10) (150 mg, 0.387 mmol) in ahydrous THF (2.5 mL) at 0° C. was added trifluoromethyltrimethylsilane (121 μL, 0.774 mmol) and TBAF (100 μL in THF and 5% water). The reaction was stirred to room temperature for 3 hours. Then TBAF (0.5 mL in THF and 5% water) was added and the reaction was stirred for 1 hour. The solvent was concentrated and the crude product was dissolved in ethyl acetate. The organic phase was washed with a water, brine and dried over anhydrous sodium sulfate. The crude product was purified by silica chromatography to yield N-(5-(5-(3-hydroxy-3-(trifluoromethyl)cyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (F25). 1H NMR (400 MHz, d6-DMSO) δ 10.04 (s, 1H), 9.47-9.45 (m, 1H), 8.60 (s, 1H), 8.09 (d, J=1.6 Hz, 1H), 7.83 (dd, J=2.0, 8.0 Hz, 1H), 7.80-7.78 (m, 1H), 7.55-7.50 (m, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.20-7.16 (m, 1H), 6.92 (s, 1H), 3.32-3.28 (m, 1H), 2.99-2.93 (m, 2H), 2.68-2.60 (m, 2H), 2.37 (s, 3H). MS m/z 458.41 (M+1)+.

Provenance & Evidence