Sodium Carbonate → HCID 57420250, compound

Participants

Reaction Conditions

Reaction Steps

A dry flask containing 4-amino-2-morpholinobenzonitrile (46.5 mg, 0.23 mmol) in dry DMF (2.0 mL) was cooled to 0° C., then potassium tert-butoxide (78.8 mg, 0.70 mmol) was added carefully in portions. The mixture was stirred at 0° C. for 15 minutes, then 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (74.7 mg, 0.26 mmol) was added in portions. Upon complete addition, the mixture was warmed to 100° C. After 2.5 h, the reaction was cooled to rt then was carefully treated with 10% sodium carbonate solution. The black mixture was subsequently extracted five times with DCM:methanol (90:10). The organic extraction was 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 a 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-(5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-2-morpholinobenzonitrile. 1H NMR (500 MHz, CDCl3) δ ppm 8.74 (1H, d, J=4.6 Hz), 7.97 (2H, m), 7.72 (1H, m), 7.47 (1H, d, J=8.3 Hz), 7.44 (1H, m), 7.11 (2H, m), 6.44 (2H, m), 3.96 (4H, m), 3.26 (4H, m), 2.24 (3H, s). Mass Spectrum (pos.) m/e: 458.0 (M+H)+.

Provenance & Evidence