Cesium carbonate → HCID 86712706, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 2-(2-((2-chloro-5-methoxypyrimidin-4-yl)ethynyl)phenyl)acetate (A98) (0.10 g, 0.32 mmol) in 1,4-dioxane (6 mL) was added tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate (0.087 g, 0.32 mmol), Cs2CO3 (0.41 g, 1.3 mmol), Pd2(dba)3 (0.030 g, 0.032 mmol) and Xantphos (0.055 g, 0.095 mmol). The resulting mixture was degassed with nitrogen for 5 minutes, before heating under microwave irradiation for 30 minutes at 120° C., then for 60 minutes at 120° C. EtOAc (100 mL) was added and the mixture was washed with water (2×25 mL), brine (25 mL), dried (MgSO4) and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-25% EtOAc in petroleum benzine 40-60° C.) to give the title compound A99 as a yellow oil (0.11 g, 64%); 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.43-7.29 (m, 3H), 7.16 (d, J=8.5 Hz, 2H), 6.98 (s, 1H), 4.38-4.17 (m, 2H), 4.02 (s, 2H), 3.94 (s, 3H), 3.70 (s, 3H), 2.80 (t, J=11.9 Hz, 2H), 2.62 (tt, J=12.0, 3.3 Hz, 1H), 1.82 (d, J=13.0 Hz, 2H), 1.68-1.51 (m, peak obscured), 1.49 (s, 9H). LCMS-A: rt 6.69 min; m/z 557.3 [M+H]+.

Provenance & Evidence