7-Chloro-8-iodo-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine → 7-Chloro-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine-8-carbonitrile

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Reaction Steps

A 2.0-5.0 mL microwave vial was charged with 7-chloro-8-iodo-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine (30 mg, 0.083 mmol) dissolved in DMF (832 μl). To that stirring solution was added dicyanozinc (5.86 mg, 0.050 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (28.8 mg, 0.025 mmol). The vial was sealed and degassed using sonication and ultra pure argon for 1 min. After which the vial was placed into a reaction block preheated to 120° C. After 5 hours, LCMS showed a good proportion of desired product by mass (m/z=260 [M+H]+Methanol/Water/Ammonium Acetate Phenomenex Luna C18, 30×2 mm, 3u ES+/−). The mixture was cooled to rt and diluted with sat'd sodium bicarbonate and EtOAc. The organic was washed with brine, dried with magnesium sulfate, concentrated under reduced pressure, and purified by flash chromatography: (4 g, equilibrated with none, loaded with DCM, initial waste: 0 mL, fraction size: 12 mL 16×100 mm, and eluted with EtOAc in hexanes 0% [20 mL], 0-100% [120 mL]). Collected fractions to give 7-chloro-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine-8-carbonitrile (18.5 mg, 86% yield) as a plaque white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.16 (d, J=7.3 Hz, 1H), 7.78 (s, 1H), 7.06 (d, J=7.3 Hz, 1H), 3.78 (q, J=9.8 Hz, 2H).

Provenance & Evidence