反应详情

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.02 g, 0.10 mmol), polystyrene supported-triphenylphosphine (0.12 g, 0.24 mmol, 1.92 mmol/g), diisopropyl hydrazine-1,2-dicarboxylate (0.04 g, 0.19 mmol), and isopropanol (0.01 g, 0.21 mmol) were suspended in THF (1.0 mL). The reaction was allowed to shake at ambient temperature for 48 hours. The reaction mixture was filtered, the eluent was collected and concentrated under reduced pressure. Pd(dppf)Cl2 (0.011 g, 0.015 mmol), N-(3-bromo-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine (0.03 g, 0.08 mmol), sodium carbonate (0.10 mL, 0.20 mmol, 2 M) suspended in THF (1.0 mL) were added. The vial was capped and irradiated in a microwave for 15 minutes at 110° C. Silica supported-DMT (0.055 g, 0.05 mmol, 0.94 mmol/g) was added, the vial was sealed and allowed to stir for 4 hours. The reaction mixture was passed through a syringe filter, the eluent was collected and concentrated under reduced pressure. The residue was purified by reverse phase HPLC (0 to 95% ACN/water with 0.1% TFA modifier) to afford N-(3-(1-isopropyl-1H-pyrazol-4-yl)-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine. MS ESI calc'd for C18H19F3N5 [M+H]+ 362. found 362. 1H NMR (500 MHz, DMSO-d6) δ 10.10 (s, 1H), 8.80 (d, J=4.8, 1H), 8.08 (s, 1H), 7.84 (s, 1H), 7.71 (s, 1H), 7.29 (s, 1H), 7.23 (d, J=4.9, 1H), 7.07 (s, 1H), 4.49 (dt, J=6.6, 13.3, 1H), 2.28 (s, 3H), 1.43 (d, J=6.7, 6H).

1. filtrationThe reaction mixture was filtered
2. customthe eluent was collected
3. concentrationconcentrated under reduced pressure
4. additionwere added
5. customThe vial was capped
6. customirradiated in a microwave for 15 minutes at 110° C
7. additionSilica supported-DMT (0.055 g, 0.05 mmol, 0.94 mmol/g) was added
8. customthe vial was sealed
9. customThe reaction mixture was passed through a syringe
10. filtrationfilter
11. customthe eluent was collected
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified by reverse phase HPLC (0 to 95% ACN/water with 0.1% TFA modifier)