Potassium Phosphate, Tribasic → 4-(3-(5,7-Difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-5-morpholinopyridin-2-yl)phenol

Participants

Reaction Conditions

Reaction Steps

N-(2-chloro-5-morpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)-quinolin-4-amine (60.6 mg, 0.13 mmol), 4-hydroxyphenylboronic acid (36.7 mg, 0.27 mmol), tricyclohexylphosphine (7.7 mg, 0.027 mmol), and tris(dibenzylideneacetone)dipalladium (0) (12.1 mg, 0.013 mmol) were added to a flask then degassed and backfilled with argon. To the flask, 1,4-dioxane (2.0 mL) and aq. 1.3M potassium phosphate tribasic (0.3 mL, 0.39 mmol) were added by syringe. The resulting reaction was heated to 90° C. and monitored with TLC and LC-MS. After 19 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic extractions were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-55% of a premixed solution of 89:9:1 DCM:MeOH:ammonium hydroxide in DCM) to afford a film that was further purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution). The desired fractions were cond then diluted with EtOAc. After washing twice with satd aq. sodium bicarbonate solution and once with brine, the solvent was removed under reduced pressure to yield a yellow solid as 4-(3-(5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-5-morpholinopyridin-2-yl)phenol. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.49 (1H, s), 8.70 (1H, dq, J=4.8, 0.9 Hz), 8.01 (1H, td, J=7.7, 1.7 Hz), 7.94 (1H, d, J=2.4 Hz), 7.83 (1H, d, J=7.6 Hz), 7.65 (2H, m), 7.54 (4H, m), 6.79 (2H, m), 6.45 (1H, d, J=2.4 Hz), 3.76 (4H, m), 3.14 (4H, m), 2.13 (3H, s). Mass Spectrum (pos.) m/e: 526.2 (M+1).

Provenance & Evidence