Potassium Phosphate, Tribasic → N-(5-(3,6-dihydro-2H-pyran-4-yl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(5-bromo-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine (38.0 mg, 0.089 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (29.1 mg, 0.139 mmol), 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl (S-Phos) (7.7 mg, 0.019 mmol), palladium(II) acetate (6.9 mg, 10.24 μmol), and potassium phosphate tribasic (60.4 mg, 0.29 mmol) in DMF (1 mL) and water (0.05 mL) was degassed by nitrogen. The mixture was heated to 90° C. After 21.5 h, the reaction was cooled to rt, then treated with water. After extracting twice with EtOAc, the organic layers were combined and dried over anhydrous magnesium sulfate. After filtration and concentration the residue was purified on basic alumina (0-35% EtOAc in hexanes) to afford an impure yellow residue. The light yellow film was further purified by HPLC (10-60% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution.) The desired fractions were concentrated 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 white solid as N-(5-(3,6-dihydro-2H-pyran-4-yl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.76 (1H, m), 8.31 (1H, d, J=1.8 Hz), 8.18 (1H, d, J=2.5 Hz), 7.94 (2H, m), 7.69 (1H, m), 7.38 (1H, dddd, J=7.4, 4.9, 1.3, 0.7 Hz), 7.12 (3H, m), 6.25 (1H, m), 4.33 (2H, q, J=2.7 Hz), 3.94 (2H, t, J=5.5 Hz), 2.51 (2H, td, J=5.0, 2.2 Hz), 2.17 (3H, s). Mass Spectrum (pos.) m/e: 431.1 (M+1).

Provenance & Evidence