TFA (0.1 mL) was added to a solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)-5-(trifluoromethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A62) (0.170 g, 0.261 mmol) in DCM (4 mL) and the resulting mixture stirred for 24 hours at room temperature. The volatiles were evaporated under reduced pressure then the residue adsorbed onto silica gel and purified by column chromatography (SiO2, 1-50% MeOH in DCM). The volatiles were removed in vacuo and the residue dissolved in dry MeOH (5 mL). Formaldehyde (37 wt. % in H2O; 0.030 mL, 0.36 mmol) was added and the resulting mixture was stirred for 30 minutes at room temperature. Sodium triacetoxyborohydride (0.077 g, 0.362 mmol) was added under nitrogen and the resulting mixture stirred at room temperature for 2 hours. The volatiles were evaporated under reduced pressure then the residue dissolved in EtOAc and washed with 10% NaHCO3 (20 mL). The organics were dried (MgSO4) and the volatiles removed under reduced pressure. The residue was adsorbed onto silica gel, then purified by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 50-100% MeOH in EtOAc then 10% NH3 in EtOH). Further purification by semi preparative HPLC was required to give the title compound 17 as a pale cream solid (0.011 g, 26%); 1H NMR (400 MHz, d4-MeOH) δ 8.55 (s, 1H), 7.67-7.60 (m, 2H), 7.50-7.40 (m, 3H), 7.28-7.19 (m, 2H), 3.74 (s, 2H), 3.54-3.40 (m, 2H), 3.31-3.25 (m, 2H), 3.14-3.12 (m, 2H), 2.95 (t, J=11.5 Hz, 2H), 2.80 (m, 4H), 2.08 (d, J=13.8 Hz, 2H), 1.97-1.92 (m, 2H). LCMS-B: rt 4.52 min; m/z 566 [M+H]+.
