Triphenylphosphine → Tert-butyl 4-(3-methoxy-4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazine-1-carboxylate (I72) (0.350 g, 0.717 mmol) in dimethylformamide (2.5 mL) and triethylamine (0.450 mL) was added methyl 2-(2-ethynylphenyl)acetate (I4: prepared according to the procedure of Peng, C. et al.; Adv. Synth. Catal. 2008, 350, 2359-2364 or as described below) (0.137 g, 0.789 mmol), trans-dichlorobis(triphenylphosphine)palladium(II) (0.025 g, 0.036 mmol), CuI (0.014 g, 0.072 mmol) and triphenylphosphine (0.019 g, 0.072 mmol). The reaction mixture was heated under microwave irradiation at 120° C. whilst stirring for 15 minutes. The reaction mixture was diluted with ethyl acetate and water then the resulting mixture was extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with water, brine, dried (magnesium sulfate), filtered and evaporated to give a brown solid. The solid was purified by flash column chromatography on silica gel (10-50% ethyl acetate/petroleum ether) to give the title compound (I5) (0.360 g, 80%) as an orange crystalline solid; 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 3.11 (s, 4H), 3.60 (s, 4H), 3.71 (d, 3H, J=1.0 Hz), 189 (s, 3H), 3.96 (s, 2H), 6.55 (s, 1H), 6.59 (s, 1H), 7.26-7.45 (m, 3H), 7.68 (d, 1H, J=7.6 Hz), 7.83 (s, 1H), 827 (d, 1H, J=7.3 Hz), and 8.60 (s, 1H). LCMS Method B: rt 9.55 min; m/z 626.4 [M+H]+.

Provenance & Evidence