反应详情

温度

150 °C

In a 25 mL sealable tube under nitrogen were combined 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (80 mg, 0.21 mmol) and (2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)boronic acid (50 mg, 0.32 mmol) in DME/water (3 ml:1 ml). PdCl2(dppf)-CH2Cl2 adduct (8.74 mg, 0.011 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (53.9 mg, 0.64 mmol) was added, the vessel was sealed, and reaction mixture was heated in a microwave at 150° C. for 30 min. After cooling, 2 mL of water was added to the black mixture and solids that precipitated were filtered. DCM/MeOH (1:1) was added, the mixture was pre-absorbed on silica gel and purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated product was treated with EtOH/EtOAc (1:1) and sonicated. The solids that precipitated were filtered, washed with EtOH and DCM, and dried to afford the title compound (41 mg, 42%) as a light grey solid. LCMS E-S (M+H)=449.9. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.58 (s, 1H), 11.52 (br. s., 1H), 11.47 (s, 1H), 8.75 (t, J=5.05 Hz, 1H), 8.36 (s, 1H), 8.31 (s, 1H), 8.23 (s, 1H), 5.90 (s, 1H), 5.27 (quin, J=6.69 Hz, 1H), 4.37 (d, J=5.05 Hz, 2H), 2.23 (s, 3H), 2.13 (s, 3H), 1.52 (s, 3H), 1.50 (s, 3H).

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. customreaction mixture
5. temperatureAfter cooling
6. customthat precipitated
7. filtrationwere filtered
8. additionDCM/MeOH (1:1) was added
9. customthe mixture was pre-absorbed on silica gel
10. custompurified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH)
11. additionThe isolated product was treated with EtOH/EtOAc (1:1)
12. customsonicated
13. customThe solids that precipitated
14. filtrationwere filtered
15. washwashed with EtOH and DCM
16. customdried