Trifluoroacetic acid → 2-(4-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyrimidin-5-yl)acetamide

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Reaction Steps

tert-Butyl 4-(4-((4-(2-(5-(2-amino-2-oxoethyl)pyrimidin-4-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I114) (0.076 g, 0.13 mmol) was dissolved in DCM (5 mL) under an atmosphere of nitrogen. Trifluoroacetic acid (0.298 mL, 3.89 mmol) was added to the solution and the reaction was stirred at room temperature for 23 hours. Volatiles were removed in vacuo, EtOAc (70 mL) and 2 M aq. NaOH (70 mL) were added to the residue and the layers were separated. The aqueous layer was extracted with EtOAc (2×70 mL), the combined organics were washed with brine (2×50 mL), dried (MgSO4), filtered and concentrated in vacuo to give a pale yellow gum. Methanol (˜5 mL) and cyclohexane (˜15 mL) were added to the product, some of the volatiles were removed in vacuo (˜50%) which gave a yellow oil that separated from the solvent solution and was carefully transferred to a new flask with a pipette. The removed solution was concentrated in vacuo and then further dried under high-vacuum to give a pale yellow gum. Diethyl ether (5 mL) and methanol (1 mL) were added and the solution was concentrated in vacuo. The process was repeated twice with diethyl ether to give the title compound (29) (35 mg, 56% yield) as a pale yellow solid; 1H NMR (400 MHz, d4-MeOD) δ 8.91 (s, 1H), 8.53-8.50 (m, 2H), 7.52 (d, J=8.2 Hz, 2H), 7.21-7.16 (m, 2H), 3.70 (s, 2H), 3.42-3.34 (m, 4H), 3.27-3.20 (m, 2H), 2.84 (td, J=12.5, 2.6 Hz, 2H), 2.70 (tt, J=12.2, 3.9 Hz, 1H), 1.89 (d, J=13.7 Hz, 2H), 1.72 (ddd, J=16.4, 12.9, 4.0 Hz, 2H). LCMS Method C: rt 4.46 min; m/z 486.1 [M+H]+.

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