反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
实验步骤: 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 (200.0 mg, 0.3183 mmol), piperazine-1-acetic acid tert-butyl ester (382 mg, 1.91 mmol), bis(dibenzylideneacetone)palladium (58.29 mg, 0.06366 mmol), 2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (118.9 mg, 0.1910 mmol), Cs2CO3 (0.3111 g, 0.9548 mmol) in 1,4-dioxane (20 mL) was evacuated and purged with nitrogen three times. The mixture was stirred at 100° C. for 2 days. The crude mixture was purified by MDP. The purified ester was taken up in methylene chloride (1.2 mL) and trifluoroacetic acid (0.6 mL) and the mixture was stirred at room temperature for 3 hours. The crude product was purified by MDP to obtain the title compound as a trifluoroacetic acid salt. 1H NMR (400 MHz, methanol-d4) δ=1.27 (t, J=7.1 Hz, 6 H), 3.19 (s, 3 H), 3.29 (d, J=21.5 Hz, 2 H), 3.41 (br. s., 4 H), 3.60 (br. s., 4 H), 4.07 (qd, J=7.2, 6.9 Hz, 4 H), 4.17 (s, 2 H), 4.51 (s, 2 H), 7.26 (d, J=9.1 Hz, 1 H), 7.34 (d, J=6.6 Hz, 2 H), 7.57 (d, J=7.8 Hz, 2 H), 8.36 (s, 1 H), 8.69 (br. s., 1 H). MS (ES+): m/z 692.27 (100) [MH+]; HPLC: tR=0.78 min (UPLC, purity).
was evacuated
purged with nitrogen three times
The crude mixture was purified by MDP
trifluoroacetic acid (0.6 mL) and the mixture was stirred at room temperature for 3 hours
The crude product was purified by MDP
来源 ID: ord-568e837218e047cab6d3a01932a91e45