反应详情

温度

120 °C

(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.74 mg, 6.46 μmol), 7-iodo-2-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-2H-pyrazolo[4,3-b]pyridine (100 mg, 0.258 mmol), Pd2(dba)3 (5.91 mg, 6.46 μmol), 3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-amine (56.1 mg, 0.258 mmol) and sodium 2-methylpropan-2-olate (74.5 mg, 0.775 mmol) were combined in dioxane (5 mL) and heated at 120° C. for 1 hour. The reaction was then cooled, concentrated, and purified by prep-HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 10-50% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to give a residue which was combined with 1N HCl (4 mL) and stirred at room temperature for 1 hour before the solvent was removed to give the title compound as a hydrochloride salt. 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.14 (t, J=6.19 Hz, 2H) 2.68 (s, 3H) 2.71 (s, 3H) 3.52 (t, J=5.94 Hz, 2H) 4.68 (t, J=6.95 Hz, 2H) 7.54 (d, J=6.57 Hz, 1H) 7.64 (dd, J=8.59, 3.54 Hz, 1H) 7.82 (dd, J=11.37, 8.59 Hz, 1H) 8.53 (s, 1H) 8.71 (d, J=6.57 Hz, 1H) 8.86 (s, 1H) 8.90 (s, 1H). MS [M+H] found 393.4.

1. temperatureThe reaction was then cooled
2. concentrationconcentrated
3. custompurified
4. washeluting with a gradient of 10-50% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA)
5. customto give a residue which
6. customwas removed