反应详情

温度

25 °C

To a pale yellow solution of 3-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (43 mg, 86.2 μmol) in dichloromethane (2.00 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol51), the reaction mixture turned dark red and was stirred at 25° C. overnight then concentrated. 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 3 h, then evaporated to a light yellow solid, dissolved in dichloromethane (added few drops MeOH and heating) and purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 10% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane. Pure white solid product was sonicated with hexanes. The solid was separated by decantation and dried under high vacuum to give 3-(7-(tert-butylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (28 mg, 76.0 mmol, 88.1%) as a white solid. MS (M+H)+=369.1 (100% purity); 1H NMR (DMSO-d6) δ: 12.88 (br. s., 1H), 8.87 (s, 1H), 8.40 (s, 1H), 7.32 (s, 1H), 3.35 (s, 3H), 2.36-2.46 (m, 2H), 2.03 (br. s., 2H), 1.86-1.96 (m, 4H), 1.44 (s, 9H).

1. concentrationthen 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 3 h
4. customevaporated to a light yellow solid
5. dissolutiondissolved in dichloromethane (added few drops MeOH and heating)
6. custompurified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
7. washeluting with 0 to 10% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane
8. customwas sonicated with hexanes
9. customThe solid was separated by decantation
10. customdried under high vacuum