反应详情

温度

85 °C

A mixture of ((S)-1-{5-bromo-3-[(S)-1-(2,6-dichloro-3-fluorophenyl)ethyl]pyrrolo[2,3-b]pyridine-1-carbonyl}-3-methylbutyl)-carbamic acid 9H-fluoren-9-ylmethyl ester (190.0 mg, 0.262 mmol), 1-[2-(tetrahydropyran-2-yloxy)ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (95.0 mg, 0.294 mol), Pd(PPh3)4 (20 mg, 0.010 mmol), potassium carbonate (181 mg, 1.31 mmol) in a mixed solvent of dioxane and water (v:v=4:1, dioxane:H2O, 10 mL) was heated to 85° C. for 1 h. The organic solvent was removed and the material was transferred to a separatory funnel and extracted with DCM (20 mL×3). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo to give a residue that was re-dissolved in dioxane (4 mL). 2M aq. HCl (1.0 mL) was added at rt, and the solution was allowed to stir for 1 h. The solvents were removed in vacuo, and the material was dry-loaded onto silica gel for column chromatography, eluting with 3-4% (7N NH3 in MeOH)/DCM to reveal the title compound. MS (ES+): m/z=419.21, 421.19 (100, 85) [MH+]. HPLC: tR=0.92 min (HPLC-ACQUITY, Purity).

1. customThe organic solvent was removed
2. customthe material was transferred to a separatory funnel
3. extractionextracted with DCM (20 mL×3)
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated in vacuo
6. customto give a residue that
7. customThe solvents were removed in vacuo
8. washeluting with 3-4% (7N NH3 in MeOH)/DCM