反应详情

温度

80 °C

2-(6-Chloro-1-((1-methyl-1H-imidazol-2-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (106 mg, 183 μmol) was dissolved in dichloroethane (10 mL). To this mixture was added trifluoroacetic acid (2.09 g, 1.41 mL, 18.3 mmol) and the mixture was heated to 80° C. After 15 h, the mixture was concentrated in vacuo. The residue was dissolved in 60:20:1 dichloromethane:methanol:ammonium hydroxide (10 mL). After 2 h the mixture was concentrated in vacuo, then purified by chromatography (silica, Analogix 40 g, 0-5% methanol in dichloromethane, over 15 min) to give 2-(6-chloro-1-((1-methyl-1H-imidazol-2-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (87 mg, 194 μmol, 106%) as a yellow powder. MS (M+H)+=449; 1H NMR (CDCl3) δ: 11.90-12.06 (m, 1H), 8.97-9.07 (m, 1H), 8.27-8.35 (m, 1H), 8.11-8.17 (m, 1H), 7.95-8.05 (m, 1H), 7.72-7.82 (m, 1H), 7.05-7.13 (m, 1H), 6.94-7.03 (m, 1H), 6.81-6.92 (m, 1H), 5.69-5.83 (m, 2H), 4.17-4.38 (m, 1H), 3.72 (s, 3H), 1.24 (d, J=6.4 Hz, 6H).

1. concentrationthe mixture was concentrated in vacuo
2. dissolutionThe residue was dissolved in 60:20:1 dichloromethane
3. concentrationAfter 2 h the mixture was concentrated in vacuo
4. custompurified by chromatography (silica, Analogix 40 g, 0-5% methanol in dichloromethane, over 15 min)