反应详情

To a slightly yellow clear solution of N-isopropyl-2-(1-methyl-5-(trifluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (113 mg, 206 μmol) in dichloromethane (5 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol), the reaction mixture was stirred 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 (containing a few drops of MeOH) and purified by chromatography (40 g column, 50 μm from Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide)/dichloromethane). The pure product was suspended in dichloromethane and cyclohexane added to promote solid formation, then the solid was separated by filtration and dried to give N-isopropyl-2-(1-methyl-5-(trifluoromethoxy)-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (78 mg, 186 μmol, 91%) as a white solid. MS (M+H)+=419; 1H NMR (DMSO-d6) δ: 12.86 (br. s., 1H), 9.12 (s, 1H), 8.42 (s, 1H), 8.34 (s, 1H), 7.88-7.97 (m, 2H), 7.56 (d, J=9.1 Hz, 1H), 4.14-4.36 (m, 4H), 1.30 (d, J=6.4 Hz, 6H).

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 (containing a few drops of MeOH)
6. custompurified by chromatography (40 g column, 50 μm from Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide)/dichloromethane)
7. additioncyclohexane added
8. customthe solid was separated by filtration
9. customdried