Cesium carbonate → tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)phenoxy)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 2-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)acetamide (K6) (0.150 g, 0.518 mmol), tert-butyl 4-(4-aminophenoxy)piperidine-1-carboxylate (A112) (0.182 g, 0.621 mmol), Pd(OAc)2 (2.3 mg, 0.010 mmol), Cs2CO3 (0.506 g, 1.55 mmol) and Xantphos (12 mg, 0.021 mmol) in 1,4-dioxane (2 mL) was heated under microwave irradiation at 100° C. for 45 minutes. Water (20 mL) and EtOAc (20 mL) were added and the resulting suspension sonicated for 1 minute and then filtered through Celite. The resulting mixture was extracted with EtOAc (×2) and the combined organic extracts were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified using silica gel column chromatography (CombiFlash Rf, 12 g SiO2 cartridge, 0-10% MeOH in DCM) to give the title compound A113 as a light pink colored foam (50 mg, 18%); 1H NMR (300 MHz, d4-MeOH) δ 8.04 (s, 1H), 7.52 (d, J=8.9 Hz, 2H), 7.18-7.27 (m, 5H), 6.92 (d, J=9.0 Hz, 2H), 4.47-4.52 (m, 1H), 4.10-4.13 (m, 2H), 3.67-3.77 (m, 2H), 3.65 (s, 3H), 3.37 (m, 2H), 3.09-3.15 (m, 2H), 2.93-2.98 (m, 2H), 1.91-2.03 (m, 2H), 1.64-1.78 (m, 2H), 1.51 (s, 9H). LCMS-B: rt 7.302 min; m/z 546 [M+H]+.

Provenance & Evidence