反应详情

温度

25 °C

To a pale yellow solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-morpholinopropyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (62 mg, 94.2 μmol) in dichloromethane (4.00 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol38), the reaction mixture turned orange and was stirred at 25° C. for 18 h, mixture concentrated and the residue was re-dissolved in 5 mL of a solution of (dichloromethane/MeOH/ammonium hydroxide; 60:10:1) and stirred at 25° C. for 1 h, then evaporated to a yellow solid, which was dissolved in dichloromethane and purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane. The pure product dissolved in dichloromethane with few drops of MeOH and cyclohexane added to allow solid formation, light yellow flakes were separated by decantation and dried under high vacuum to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-morpholinopropyl)-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (45 mg, 85.3 μmol, 90.5%). MS (M+H)+=528; 1H NMR (DMSO-d6) δ: 12.80 (br. s., 1H), 9.06 (s, 1H), 8.37 (s, 1H), 8.19 (s, 1H), 7.77-7.98 (m, 2H), 7.38 (d, J=8.7 Hz, 1H), 7.18 (t, J=74.4 Hz, 1H), 4.57 (t, J=5.7 Hz, 2H), 3.49 (br. s., 4H), 2.26 (br. s., 6H), 2.00-2.15 (m, 2H), 1.49 (s, 9H).

1. concentrationmixture concentrated
2. dissolutionthe residue was re-dissolved in 5 mL of a solution of (dichloromethane/MeOH/ammonium hydroxide; 60:10:1)
3. stirringstirred at 25° C. for 1 h
4. customevaporated to a yellow solid, which
5. dissolutionwas dissolved in dichloromethane
6. custompurified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
7. washeluting with 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane
8. dissolutionThe pure product dissolved in dichloromethane with few drops of MeOH and cyclohexane
9. additionadded
10. customwere separated by decantation
11. customdried under high vacuum