Hydrochloric Acid → Phenylmethyl 4-([4-({4-[2-(3-cyanophenyl)imidazo[1,2-a]pyridin-3-yl]-2-pyrimidinyl}amino)-3-methylphenyl]oxy}-1-piperidinecarboxylate

Participants

Reaction Steps

3-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzonitrile (Intermediate Example 5) (0.462 g, 1.39 mmol) and phenylmethyl 4-[(4-amino-3-methylphenyl)oxy]-1-piperidinecarboxylate (0.567 g, 1.67 mmol) were dissolved in 16 mL of trifluoroethanol with stirring in a pressure vessel. HCl (4N in dioxane, 0.17 mL, 0.68 mmol) was added via syringe. The vessel was sealed and placed in an 80° C. oil bath. The reaction was stirred at 80° C. for 40 h and cooled to rt. The reaction 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. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 0.700 g (79%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.25 (br. s., 1H), 8.90 (s, 1H), 8.20 (d, J=5.1 Hz, 1H), 8.04 (s, 1H), 7.96-7.86 (m, 2H), 7.72-7.61 (m, 2H), 7.46-7.21 (m, 7H), 6.93-6.79 (m, 3H), 6.41 (d, J=5.3 Hz, 1H), 5.06 (s, 2H), 4.59-4.50 (m, 1H), 3.77-3.65 (m, 2H), 3.36-3.21 (m, 2H), 2.18 (s, 3H), 1.97-1.86 (m, 2H), 1.61-1.49 (m, 2H).

Provenance & Evidence