Cesium carbonate → HCID 58292935, compound

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)-3-methoxybenzyl]phosphonate (200.0 mg, 0.3038 mmol), 1-methylpiperazine (202 uL, 1.82 mmol), bis(dibenzylideneacetone)palladium(0) (34.9 mg, 0.0608 mmol), Cs2CO3 (297 mg, 0.911 mmol) in 1,4-dioxane (20 mL) was evacuated and purged with nitrogen three times and allowed to stir at 100° C. overnight. The reaction mixture was passed through a Thiol-SPE cartridge to remove Pd and the crude material was purified by MDP. The resulting material, diethyl (3-methoxy-4-{[4-{[2-methyl-7-(4-methylpiperazin-1-yl)-3-oxo-2,3-dihydro-1H-isoindol-4-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl) phosphonate, was taken up in conc. HCl (2.0 mL) and heated at 80° C. for 2 hours. The crude material was again purified by MDP to obtain the title compound (2.3 mg, 1.2% yield). 1H NMR (400 MHz, methanol-d4) δ=1.26 (t, J=6.9 Hz, 3 H), 2.99 (s, 3 H), 3.17 (s, 3 H), 3.18 (d, J=20.7 Hz, 2 H), 3.24-3.29 (m, 2 H), 3.33-3.36 (m, 2 H), 3.38-3.46 (m, 2 H), 3.58 (br. s., 2H), 3.88 (s, 3 H), 4.03 (quin, J=7.1 Hz, 2 H), 4.48 (s, 2 H), 7.00 (d, J=8.1 Hz, 1 H), 7.10 (s, 1H), 7.21 (d, J=8.8 Hz, 1 H), 7.60 (d, J=7.6 Hz, 1 H), 8.32 (s, 1 H), 8.39 (br. s., 1 H). MS (ES+): m/z 650.29 (100) [MH+]; HPLC: tR=0.63 min (UPLC, purity).

Provenance & Evidence