Cesium carbonate → Diethyl (4-{[4-{[7-(4-acetyl piperazin-1-yl)-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Participants

Reaction Conditions

Reaction Steps

A mixture of Diethyl[4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate (50.0 mg, 0.0796 mmol), 1-acetylpiperazine (0.510 g, 3.98 mmol), bis(dibenzylideneacetone)palladium(0) (9.15 mg, 0.0159 mmol), and Cs2CO3 (77.8 mg, 0.239 mmol) in 1,4-dioxane (5 mL) was evacuated and purged with N2 three times and stirred at 100° C. overnight. The crude mixture was passed through a Thiol-SPE cartridge to remove Pd and subsequently purified by MDP to isolate the title compound (10.5 mg, 20% yield). 1H NMR (400 MHz, CD3OD) δ=1.28 (t, J=7.1 Hz, 6H), 2.17 (s, 3H), 3.04-3.10 (m, 2H), 3.11-3.15 (m, 2H), 3.19 (s, 3H), 3.23 (d, J=21.5 Hz, 2H), 3.68-3.73 (m, 2H), 3.73-3.79 (m, 2H), 4.02-4.14 (m, 4H), 4.54 (s, 2H), 7.15 (d, J=8.8 Hz, 1H), 7.38 (dd, J=8.6, 2.5 Hz, 2H), 7.53 (d, J=8.1 Hz, 2H), 8.34 (s, 1H), 8.52 (br. s., 1H).

Provenance & Evidence