1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → (S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-N-(3'-fluoro-6'-methyl-2,2'-bipyridin-4-yl)-1H-pyrazolo[4,3-b]pyridin-7-amine

Participants

Reaction Conditions

Reaction Steps

(S)-2-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-7-iodo-2H-pyrazolo[4,3-b]pyridine (51 mg, 0.142 mmol), Tris(dibenzylideneacetone)dipalladium(0) (3.25 mg, 3.55 μmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20.54 mg, 0.035 mmol), 3′-fluoro-6′-methyl-2,2′-bipyridin-4-amine (28.9 mg, 0.142 mmol) and sodium 2-methylpropan-2-olate (40.9 mg, 0.426 mmol) were combined in dioxane (5 mL). The mixture was heated at 120° C. for 2 hours, then cooled and purified by preparative HPLC using a Phenomenex Gemini Prep 5 μm C18, 75×30 mm column eluting with a gradient of 5-40% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to give (S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-N-(3′-fluoro-6′-methyl-2,2′-bipyridin-4-yl)-1H-pyrazolo[4,3-b]pyridin-7-amine which was combined with methanol (5 mL) and 1N HCl (2 mL) and stirred at room temperature for 30 minutes before evaporation to afford the title compound (12.5 mg, 22.32% yield) as a HCl salt. 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.57 (s, 3H) 3.41 (m, 1H) 3.49 (m, 1H) 3.97-4.10 (m, 1H) 4.51 (m, 1H) 4.69 (m, 1H) 7.51 (dd, J=8.59, 3.54 Hz, 1H) 7.64 (d, J=6.32 Hz, 1H) 7.71 (dd, J=11.24, 8.72 Hz, 1H) 8.01 (d, J=5.05 Hz, 1H) 8.53 (s, 1H) 8.63 (d, J=6.32 Hz, 1H) 8.66-8.71 (m, 2H). MP 182-184° C. MS [M+H] found 395.3.

Provenance & Evidence