Triethylamine → tert-Butyl 4-(4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate (I94) (0.500 g, 1.06 mmol) and methyl 2-(2-ethynylphenyl)acetate (I4) (0.203 g, 1.17 mmol) were dissolved in DMF (10 mL) and bis(triphenylphosphine)palladium(II) chloride (37 mg, 5 mol %) was added. The mixture was degassed with nitrogen for ten minutes, then copper(I) iodide (10 mg, 5 mol %) and triethylamine (0.738 mL, 5.30 mmol) were added. The mixture was heated under microwave irradiation (100° C./20 minutes) then concentrated. Chromatography of the residue (12 g silica cartridge, 0-100% ethyl acetate/petroleum benzine 40-60° C.) gave the title compound (I95) (192 mg, 30% yield) as a brown oil; 1H NMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 7.68 (dd, J=7.6, 1.0 Hz, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.50 (s, 1H), 7.42 (dd, J=7.5, 1.4 Hz, 1H), 7.38-7.29 (m, 4H), 3.95 (s, 2H), 3.70 (s, 3H), 3.50 (s, 2H), 3.45-3.40 (m, 4H), 2.43-2.35 (m, 4H), 1.45 (s, 9H). LCMS Method C: rt 5.30 min; m/z 610.1 [M+H]+, m/z 608.2 [M−H]−.

Provenance & Evidence