反应详情

To a solution of N-[3-(2-chloro-pyrimidin-4-ylethenyl)-phenyl]-2,2,2-trifluoro-acetamide (See Example 1, step B) (5.0 g) in DMF (40 mL) were added 1-amino-3-fluoropyridinium nitrate (5.4 g) and K2CO3 (6.0 g). The reaction was kept stirring at RT for 1.5 h. The DMF solution was poured into 5% LiCl solution (60 mL) and extracted with EtOAc (2×30 mL). The combined organic phase were dried (Na2SO4) and concentrated. The crude products were separated through silica gel column chromatography to afford two products. The first to elute was N-{3-[3-(2-chloro-4-pyrimidinyl)-6-fluoropyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide (2.0 g, 30% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.08 (d, 1H, J=5.49 Hz), 7.45 (d, 1H, J=7.68 Hz), 7.55 (t, 1H, J=7.96 Hz), 7.73-7.79 (m, 1H), 7.83 (d, 1H, J=0.91 Hz), 7.95 (t, 1H, J=1.74 Hz), 8.41 (dd, 1H, J=9.97, 5.76 Hz), 8.49 (d, 1H, J=5.49 Hz), 9.27 (dd, 1H, J=4.30, 2.29 Hz). ES-LC/MS m/z=436 [M+H]+.

1. extractionextracted with EtOAc (2×30 mL)
2. dry with materialThe combined organic phase were dried (Na2SO4)
3. concentrationconcentrated
4. customThe crude products were separated through silica gel column chromatography
5. customto afford two products
6. washThe first to elute