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

Participants

Reaction Conditions

Reaction Steps

A mixture of 7-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine and 7-iodo-2-methyl-2H-pyrazolo[4,3-b]pyridine (162 mg, 0.625 mmol), 3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-amine (136 mg, 0.625 mmol), tris(dibenzylideneacetone)dipalladium(0) (28.6 mg, 0.031 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (18.09 mg, 0.031 mmol) and sodium 2-methylpropan-2-olate (180 mg, 1.876 mmol) were combined in dioxane (15 mL) and heated at 110° C. for 15 minutes. The solvent was then removed in vacuo to give a residue which was purified by preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 30-35% acetonitrile (containing 10 mM NH4HCO3) in water (containing 10 mM NH4HCO3) to give N-(3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-yl)-2-methyl-2H-pyrazolo[4,3-b]pyridin-7-amine: 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.84 (s, 3H) 0.91 (s, 3H) 1.72 (br. s., 1H) 2.54 (s, 3H) 5.58 (s, 1H) 5.62 (d, J=4 Hz, 1H) 5.72 (dd, J=12, 4 Hz, 1H) 5.94 (dd, J=12, 8 Hz, 1H) 6.58 (s, 1H) 6.80 (s, 1H) 6.83 (d, J=4 Hz, 1H). Melting point 102.9-103. Fractions were combined and further purified by a second preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 15-35% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to give N-(3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-yl)-1-methyl-1H-pyrazolo[4,3-b]pyridin-7-amine as a TFA salt. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.90 (s, 3H) 0.98 (s, 3H) 1.54-1.64 (m, 1H) 2.63 (s, 3H) 5.59 (d, J=8 Hz, 1H) 5.87 (dd, J=12, 4 Hz, 1H) 6.06 (dd, J=12, 8 Hz, 1H) 6.69 (s, 1H) 6.90 (d, J=8 Hz, 1H) 7.00 (s, 1H) 7.09 (s, 1H).

Provenance & Evidence