Sodium t-butoxide → 4-[4-Methyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-4-ylamino)-phenylsulfanyl]-phenol

Participants

Reaction Steps

A mixture of the product of Example 8c (62.1 mg, 0.371 mmol), the product of Example 6c (85.7 mg, 0.371 mmol), Pd2(dba)3 (16.9 mg, 0.0185 mmol), sodium t-butoxide (89.0 mg, 0.926 mmol), and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicycl[3,3,3]undecane (25.4 mg, 0.0741 mmol) in toluene (3 mL) was degassed, left under a positive pressure of nitrogen, and heated under reflux for 2 h. Additional amounts of Pd2(dba)3 (7.0 mg, 0.0076 mmol) and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicycl[3,3,3]undecane (15 mg, 0.044 mmol) were added the reaction mixture was heated under reflux for an addition 2 h. The mixture was then cooled to room temperature and partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous phase was extracted with ethyl acetate and the combined organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with a 2-5% MeOH/CH2Cl2, gradient to provide the title compound (0.0279 g, 21% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm: 2.27 (s, 3H), 4.11 (s, 3H), 5.92 (d, J=5.15 Hz, 1H), 6.75-6.85 (m, 3H), 7.02 (dd, J=8.27, 0.92 Hz, 1H), 7.14 (s, 1H), 7.18-7.27 (m, 2H), 8.09 (d, J=5.15 Hz, 1H), 8.20 (s, 1H), 8.77 (s, 1H), 9.82 (s, 1H); MS (ESI+) m/z 363.0 (M+H)+ (ESI−) m/z 360.9 (M−H)−.

Provenance & Evidence