Formaldehyde → 2-(2-(2-(2-((4-(1-Methylpiperidin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

Participants

Reaction Steps

To a suspension of 2-(2-(2-(2-((4-piperidin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (8) (0.023 g, 0.048 mmol) in anhydrous methanol (1.5 mL) were added a 37% aq. solution of formaldehyde (0.014 mL, 0.19 mmol) and sodium triacetoxyborohydride (0.050 g, 0.24 mmol) under an atmosphere of nitrogen. The reaction was stirred at room temperature for 2.5 hours, the volatiles were removed in vacuo and the residue was diluted with EtOAc (15 mL) and sat. aq. NaHCO3 (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (10 mL), the combined organic layers were washed with water (10 mL), brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo to give a solid which was taken up in DCM (˜10 mL) and methanol (˜1 mL) and concentrated in vacuo. The process was repeated with only DCM twice after which the sample was further dried on high-vacuum to give the title compound (9) (0.022 g, 91% yield) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.17 (s, 1H), 8.66 (s, 1H), 7.68 (d, J=8.6 Hz, 2H), 7.43 (s, 1H), 7.27-7.13 (m, 6H), 6.92 (s, 1H), 3.49 (s, 2H), 3.15-2.98 (m, 4H), 2.97-2.90 (m, 1H), 2.75-2.69 (m, 1H), 2.07-1.97 (m, 1H), 1.90 (s, 3H), 1.73 (d, J=12.8 Hz, 1H), 1.66-1.54 (m, 3H), 1.50-1.38 (m, 1H), 1.36-1.27 (m, 1H). LCMS Method C: rt 4.88 min; m/z 498.3 [M+H]+.

Provenance & Evidence