反应详情

Crude tert-butyl 4-(3-amino-4-((tert-butoxycarbonyl)(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)ureido)pyrimidin-4-yl)amino)phenyl)piperazine 1-carboxylate (95 g, 0.11 mmol) was dissolved in THF (1.5 ml) and stirred over ice bath under nitrogen atmosphere. DIEA (57 μl, 0.30 mmol) followed by acryloyl chloride (13 μl, 0.16 mmol) were added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into EtOAc and brine. The organic. layer was separated, dried over MgSO4 and evaporated. The resulting material was purified by flash chromatography on silica eluting with 30% to 100% EtOAc/Hexane to afford the title compound (47 mg, yield: 47%). 1H-NMR (400 MHz, CDCl3) δ 0.02 (s, 9H) 0.79-1.04 (m, 2H) 1.36 (s, 9H) 1.49 (s, 9H) 3.08 (s, 4H) 3.05 (s, 3H) 3.25 (br. s., 4H) 3.64 (br. s., 4H) 3.86 (s, 6H) 5.27 (s, 1H) 5.67-5.79 (m, 1H) 6.15-6.56 (m, 2H) 6.48 (s, 1H) 7.03-7.14 (m, 1H) 7.87-8.09 (m, 2H) 8.19-8.29 (br. s., 1H) 8.44 (s, 1H).

1. additionwere added
2. stirringthe reaction mixture was stirred at room temperature for 1 hour
3. customlayer was separated
4. dry with materialdried over MgSO4
5. customevaporated
6. customThe resulting material was purified by flash chromatography on silica eluting with 30% to 100% EtOAc/Hexane