反应详情

温度

120 °C

In a 25 mL sealable tube under nitrogen were combined 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide (110 mg, 0.24 mmol), N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]acetamide (104 mg, 0.4 mmol) in DME/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 (10.76 mg, 0.013 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (66.4 mg, 0.79 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 120° C. for 20 min. Water was added and the solids that precipitated were filtered off. DCM was added to the solids and it was purified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH). Fractions were evaporated. EtOAc was added, it was sonicated and the solids that precipitated were filtered, washed with hexanes and dried to afford the title compound (91 mg, 72%) as a light beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 10.65 (s, 1H) 8.84 (d, J=2.27 Hz, 1H) 8.64 (t, J=4.93 Hz, 1H) 8.39 (s, 1H) 8.25-8.30 (m, 1H) 8.15-8.24 (m, 2H) 7.89-7.93 (m, 1H) 5.89 (s, 1H) 5.18 (quin, J=6.63 Hz, 1H) 4.40 (d, J=4.80 Hz, 2H) 2.22 (s, 3H) 2.13 (s, 3H) 2.12 (s, 3H) 1.51 (s, 3H) 1.50 (s, 3H). MS (ES) [M+H]+ 473.1.

1. customIn a 25 mL sealable tube under nitrogen were combined
2. customthe resulting mixture was degassed with nitrogen for 10 min
3. customthe vessel was sealed
4. customthe solids that precipitated
5. filtrationwere filtered off
6. additionDCM was added to the solids and it
7. customwas purified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH)
8. customFractions were evaporated
9. additionEtOAc was added
10. customit was sonicated
11. customthe solids that precipitated
12. filtrationwere filtered
13. washwashed with hexanes
14. customdried