反应详情

TFA (0.2 mL) was slowly added to a stirred solution of tert-butyl (2-acrylamido-4-(4-methylpiperazine-1-carbonyl)phenyl)(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-3-tert-butylcarbonyl-1-methylureido)pyrimidin-4-yl)carbamate (0.060 g, 0.0711 mmol) in dry DCM (2 mL) under argon atmosphere at 0° C. The resulting reaction mixture was allowed to warm to room temperature and stirred for 18 h. Reaction progress was monitored by LCMS, after completion of the reaction, excess solvents were removed under reduced pressure. The resulting residue was diluted with DCM and quenched with a saturated aqueous solution of NaHCO3. The aqueous layer was separated and extracted with DCM (3×10 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under vacuum to get a crude residue. The residue was purified by silica gel column chromatography to afford 70 mg of desired product with HPLC purity 35% which was then purified by preparative HPLC (Conditions: Column: Gemini NX C18 (21.2 mm×150 mm particle size 5 μm); (Mobile Phase: A; 0.1% Ammonium bicarbonate in Water, B; ACN) to afford the desired compound. The compound was then diluted with dichloromethane and water. The aqueous layer was separated and extracted with DCM (3×10 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under vacuum to afford the title compound (0.005 g, yield: 11%) as a white solid. 1H-NMR (CD3OD, 400 MHz): δ 8.41 (s, 1H), 7.79-7.76 (m, 2H), 7.36 (dd, 1H), 6.82 (s, 1H), 6.47-6.42 (m, 3H), 5.82 (d, 1H), 3.96 (s, 6H), 3.81-3.55 (m, 8H), 2.54 (s, 3H), 2.37 (s, 3H); MS (ESI): 643.1 [M+H]+; HPLC: 97.26%, rt: 6.19 min.

1. customThe resulting reaction mixture
2. customReaction progress
3. customafter completion of the reaction, excess solvents
4. customwere removed under reduced pressure
5. additionThe resulting residue was diluted with DCM
6. customquenched with a saturated aqueous solution of NaHCO3
7. customThe aqueous layer was separated
8. extractionextracted with DCM (3×10 mL)
9. washThe organic phase was washed with brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under vacuum
13. customto get a crude residue
14. customThe residue was purified by silica gel column chromatography