反应详情

温度

100 °C

A mixture of tert-butyl 4-(5′-chloro-6-fluoro-2,4′-bipyridin-2′-yl-amino)piperidine-1-carboxylate (200 mg, 0.492 mmol), DMSO (2 ml), TEA (0.137 ml, 0.983 mmol) and (3-fluorophenyl)methanamine (554 mg, 4.42 mmol) reaction mixture was flushed with argon and stirred at 100° C. for 40 hr, as the reaction mixture progress was followed by LCMS. The reaction mixture was cooled to room temperature, mixed with 150 ml of ethyl acetate, washed with saturated sodium bicarbonate (2×), water (3), saturated salt solution (1×), dried over sodium sulfate, filtered and concentrated to yield a crude material, which was purified by silica gel chromatography using a 12 g column, eluting from 0%-35% ethyl acetate with hexane. The desired fractions were collected and concentrated to constant mass, giving 225 mg of the title compound as a free base. LCMS (m/z): 512.3 (MH+), retention time=0.91 min.

1. customwas flushed with argon
2. temperatureThe reaction mixture was cooled to room temperature
3. additionmixed with 150 ml of ethyl acetate
4. washwashed with saturated sodium bicarbonate (2×), water (3), saturated salt solution (1×)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto yield a crude material, which
9. customwas purified by silica gel chromatography
10. washeluting from 0%-35% ethyl acetate with hexane
11. customThe desired fractions were collected
12. concentrationconcentrated to constant mass