Cesium carbonate → HCID 57449784, compound

Participants

Reaction Conditions

Reaction Steps

To a vial containing 5-morpholinopyridin-3-ol (67.3 mg, 0.37 mmol) in DMF (3 mL) was added cesium carbonate (0.26 g, 0.8 mmol) in portions. The mixture was stirred at 23° C. for 15 minutes, then 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (90.7 mg, 0.31 mmol) was added in portions. Upon complete addition, the mixture was warmed to 100° C. After 18 h, the reaction mixture was diluted with water then subsequently extracted five times with EtOAc. The organic extractions were then washed one time with brine and dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-45% of a premixed solution of 89:9:1 DCM:methanol:ammonium hydroxide in DCM) to afford light yellow 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 concd 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 light yellow solid as 4-(5-(5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yloxy)pyridin-3-yl)morpholine. 1H NMR (500 MHz, CDCl3) δ ppm 8.74 (1H, d, J=4.6 Hz), 8.12 (1H, d, J=2.4 Hz), 7.98 (2H, m), 7.68 (1H, dd, J=9.4, 1.3 Hz), 7.59 (1H, d, J=2.2 Hz), 7.43 (1H, sxt, J=4.4 Hz), 7.02 (1H, ddd, J=11.4, 8.9, 2.4 Hz), 6.87 (1H, s), 3.93 (4H, m), 3.29 (4H, m), 2.41 (3H, s). Mass Spectrum (pos.) m/e: 435.1 (M+H)+.

Provenance & Evidence