反应详情

温度

110 °C

In a 25 mL sealable tube under nitrogen were combined 6-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (100 mg, 0.23 mmol), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (64.2 mg, 0.29 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 adduct (9.2 mg, 0.011 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (56.6 mg, 0.67 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 110° C. for min. The mixture was evaporated, DCM/MeOH (1:1) was added, and the contents pre-absorbed on silica gel and purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH). The collected product was suspended in acetonitrile along with a few drops of EtOH and some hexanes. The contents were sonicated, and solids that precipitated were filtered and dried to afford the title compound as an off-white solid (44 mg, 42%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.55 (s, 1H) 9.21 (s, 2H) 8.63 (t, J=4.80 Hz, 1H) 8.43 (s, 1H) 8.32 (s, 1H) 7.94-7.96 (m, 1H) 5.92 (s, 1H) 5.17 (quin, J=6.63 Hz, 1H) 4.43 (br. s., 1H) 4.42 (br. s., 1H) 2.69 (s, 3H) 2.52-2.56 (m, 2H) 2.14 (s, 3H) 1.49-1.55 (m, 8H) 0.88 (t, J=7.33 Hz, 3H); LC-MS (ES) m/z=459.2

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 mixture was evaporated
5. additionDCM/MeOH (1:1) was added
6. customthe contents pre-absorbed on silica gel
7. custompurified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH)
8. customThe contents were sonicated
9. customsolids that precipitated
10. filtrationwere filtered
11. customdried