Triethylamine → tert-Butyl 4-(4-((4-((2-(2-amino-2-oxoethyl)-4-fluorophenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 2-(2-ethynyl-5-fluorophenyl)acetamide (A35) (0.114 g, 0.643 mmol), tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K5) (0.267 g, 0.585 mmol), PdCl2(PPh3)2 (0.021 g, 0.029 mmol), t-Bu3PH.BF4 (8 mg, 0.03 mmol) and CuI (6 mg, 0.03 mmol) in anhydrous DMF (4 mL) was degassed with nitrogen for 10 minutes. Et3N (1 mL) was added and the resulting mixture was heated under microwave irradiation at 120° C. for 20 minutes. The volatiles were removed under reduced pressure, then the residue adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A36 as a yellow solid (0.198 g, 57%); 1H NMR (400 MHz, d6-DMSO) δ 10.41 (s, 1H), 8.81 (s, 1H), 7.69-7.62 (m, 3H), 7.47 (s, 1H), 7.31-7.19 (m, 4H), 7.07 (s, 1H), 4.05 (s, 2H), 3.72 (s, 2H), 2.80 (s, 2H), 2.69-2.59 (m, 1H), 1.74 (d, J=13.5 Hz, 2H), 1.55-1.44 (m, 2H), 1.42 (s, 9H). LCMS-A: rt 6.554 min; m/z 596 [M−H]−.

Provenance & Evidence