Ethanol → Methyl 3-[3-(2-{[2-methyl-4-(4-piperidinyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzoate

Participants

Reaction Conditions

Reaction Steps

Phenylmethyl 4-{[4-({4-[2-(3-cyanophenyl)imidazo[1,2-a]pyridin-3-yl]-2-pyrimidinyl}amino)-3-methylphenyl]oxy}-1-piperidinecarboxylate (0.699 g, 1.10 mmol) was dissolved in 20 mL of EtOH with stirring. To the solution was added 20 mL of 2N NaOH solution. The reaction was placed in a 60° C. oil bath, and 20 mL of THF was added. The reaction was stirred at 60° C. overnight. Solid NaOH (1.6 g, 40 mmol) was added and the heat was increased to 80° C. Stirring was continued for 2.5 days, and the reaction was cooled to rt. The mixture was poured into H2O and diethyl ether, and the layers were separated. The organic layer was washed with 1N NaOH solution. The combined aqueous layers were acidified with concentrated HCl. The aqueous layer was concentrated in vacuo. The residue was dissolved in 25 mL of MeOH with stirring. Sulfuric acid (0.29 mL, 5.4 mmol) was added, and the reaction was heated to 65° C. The reaction was stirred overnight and cooled to rt. The mixture was poured into half-saturated NaHCO3 solution and DCM. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc (2×). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 0.518 g (88%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.24 (br. s., 1H), 8.87 (s, 1H), 8.21 (s, 1H), 8.17 (d, J=5.1 Hz, 1H), 8.01-7.96 (m, 1H), 7.86 (d, J=7.9 Hz, 1H), 7.69 (d, J=9.0 Hz, 1H), 7.58 (t, J=7.8 Hz, 1H), 7.46-7.38 (m, 1H), 7.22 (d, J=8.6 Hz, 1H), 6.85 (s, 2H), 6.77 (dd, J=8.5, 2.7 Hz, 1H), 6.41 (d, J=5.3 Hz, 1H), 4.39-4.28 (m, 1H), 3.84 (s, 3H), 2.97-2.87 (m, 2H), 2.49-2.59 (m, 2H), 2.17 (s, 3H), 1.93-1.83 (m, 2H), 1.48-1.35 (m, 2H).

Provenance & Evidence