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

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 2-(6-fluoro-7-iodo-2H-pyrazolo[4,3-b]pyridin-2-yl)acetylcarbamate (62 mg, 0.148 mmol) in dioxane (4 mL) was added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (21.34 mg, 0.037 mmol), Pd2(dba)3 (33.8 mg, 0.037 mmol), sodium tert-butoxide (42.5 mg, 0.443 mmol), and 3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-amine (35.3 mg, 0.162 mmol) and the mixture was heated at 110° C. for 3 hours. The solution was then cooled, diluted with water and extracted with EtOAc (3×75 mL). The combined organics were dried over Na2SO4, filtered, and concentrated to give a residue which was suspended in DMSO and purified by preparative HPLC using a gradient of 20-65% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column to give the title compound. The title compound was combined with 1N HCl (4 mL) and lyophilized to give the title compound as a hydrochloride salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.52 (s, 3H), 2.60 (s, 3H) 3.43-3.58 (m, 1H) 3.61-3.79 (m, 1H) 7.29 (d, J=2.53 Hz, 1H) 7.35 (br. s., 1H) 7.53-7.65 (m, 1H) 7.71 (br. s., 1H) 7.82 (dd, J=11.12, 8.59 Hz, 1H) 8.52 (s, 1H) 8.76 (d, J=3.03 Hz, 1H) 8.87 (s, 1H) 10.14 (br. s., 1H). MS [M+H] found 410.4.

Provenance & Evidence