Cesium carbonate → Trifluoroacetic acid

온도

100 °C

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, 6H), 3.19 (s, 3H), 3.29 (d, J=21.5 Hz, 2H), 3.41 (br. s., 4H), 3.60 (br. s., 4H), 4.07 (qd, J=7.2, 6.9 Hz, 4H), 4.17 (s, 2H), 4.51 (s, 2H), 7.26 (d, J=9.1 Hz, 1H), 7.34 (d, J=6.6 Hz, 2H), 7.57 (d, J=7.8 Hz, 2H), 8.36 (s, 1H), 8.69 (br. s., 1H). MS (ES+): m/z 692.27 (100) [MH+]; HPLC: tR=0.78 min (UPLC, purity).

1. customwas evacuated
2. custompurged with nitrogen three times
3. customThe crude mixture was purified by MDP
4. stirringtrifluoroacetic acid (0.6 mL) and the mixture was stirred at room temperature for 3 hours
5. customThe crude product was purified by MDP

ORD 기록

ord-ca3d43f8b4fc4f3c8af4f065eb636f3a

출처 데이터셋

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08399433B2