Cesium carbonate → tert-Butyl 4-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide (A14) (100 mg, 297 μmol), Cs2CO3 (291 mg, 892 μmol) and tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate (164 mg, 595 μmol) in 1,4-dioxane (2.0 mL) was sonicated for 10 min. To this Xantphos (6.88 mg, 11.9 μmol) and Pd(OAc)2 (1.33 mg, 5.95 μmol) were added and the resulting mixture heated under microwave irradiation for 20 min at 120° C. The resulting mixture was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A15 as a yellow oil (121 mg, 71%); 1H NMR (400 MHz, CDCl3) δ 8.25-8.22 (s, 1H), 7.54-7.46 (m, 3H), 7.43-7.38 (dt, J=7.4, 1.0 Hz, 1H), 7.34-7.29 (m, 2H), 7.29-7.22 (m, 1H), 7.19-7.12 (m, 2H), 5.93-5.80 (s, 1H), 5.41-5.26 (s, 1H), 4.39-4.18 (s, 2H), 3.31-3.06 (m, 4H), 2.90-2.69 (t, J=11.8 Hz, 2H), 2.69-2.54 (tt, J=12.0, 3.4 Hz, 1H), 1.88-1.68 (t, J=15.8 Hz, 4H), 1.68-1.53 (qd, J=13.0, 4.4 Hz, 2H), 1.53-1.46 (s, 9H), 1.19-1.07 (s, 2H). LCMS-A: rt 6.326 min; m/z 577 [M+H]+.

Provenance & Evidence