反应详情

温度

110 °C

To a sealed tube was added INTERMEDIATE 9 (30.0 mg, 0.072 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (16.8 mg, 0.087 mmol), Pd(dppf)Cl2—CH2Cl2 (13.2 mg, 0.018 mmol), dioxane (722 μL, 0.1 M), and aqueous Na2CO3 (90 μL, 2 M). The reaction vessel was purged with argon, sealed and heated to 110° C. for 8 hours. The completed reaction was cooled to 60° C. and to the vial was added silica bound Si-2,4,6-trimercaptotriazine (74.5 mg, 0.144 mmol, 1.94 mmol/g) as a Pd(dppf)Cl2 scavenger. The reaction was shaken for 4 hours at 60° C. The completed scavenging reaction was passed through a syringe filter and concentrated in vacuo. Purification by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v TFA modifier) afforded the title product (3M mg, 0.0065 mmol, 7.8%). MS ESI: [M+H]+ m/z 403.1. 1H NMR (500 MHz, DMSO) δ 10.27 (s, 1H), 8.83 (d, J=4.9, 1H), 8.37-8.07 (m, 1H), 8.03 (s, 1H), 7.98 (s, 1H), 7.47 (s, 1H), 7.28 (d, J=4.9, 1H), 7.18 (s, 1H), 2.32 (s, 3H). rhSTK activity=+++

1. customThe reaction vessel was purged with argon
2. customsealed
3. customThe completed reaction
4. temperaturewas cooled to 60° C. and to the vial
5. additionwas added silica
6. customThe completed scavenging reaction
7. customwas passed through a syringe
8. filtrationfilter
9. concentrationconcentrated in vacuo
10. customPurification by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v TFA modifier)