反应详情

温度

25 °C

To a solution of N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (90 mg, 181 μmol) in dichloromethane (3 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol). The reaction mixture was stirred at 25° C. overnight then concentrated. The residue was re-dissolved in 5 mL of a mixture of dichloromethane/MeOH/ammonium hydroxide (60:10:1) and stirred at 25° C. for 3 h, then evaporated to a yellow solid, dissolved in dichloromethane (containing a few drops of MeOH) and purified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane). The pure product was suspended in dichloromethane and cyclohexane added to promote solid formation. The solid was separated by decanting the mother liquors and then dried to give N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (54 mg, 147 μmol, 81%) as a white solid. MS (M+H)+=461; 1H NMR (DMSO-d6) δ: 9.11 (s, 1H), 8.37 (s, 1H), 8.17 (d, J=1.9 Hz, 1H), 7.90 (s, 1H), 7.87 (s, 1H), 7.27-7.38 (m, 2H), 7.06-7.15 (m, 1H), 6.91 (t, J=2.1 Hz, 1H), 6.80-6.89 (m, 1H), 4.20 (s, 3H), 4.11 (dq, J=13.9, 6.8 Hz, 1H), 1.06 (d, J=6.4 Hz, 6H).

1. concentrationthen concentrated
2. dissolutionThe residue was re-dissolved in 5 mL of a mixture of dichloromethane/MeOH/ammonium hydroxide (60:10:1)
3. stirringstirred at 25° C. for 3 h
4. customevaporated to a yellow solid
5. dissolutiondissolved in dichloromethane (containing a few drops of MeOH)
6. custompurified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane)
7. additioncyclohexane added
8. customThe solid was separated
9. customby decanting the mother liquors
10. customdried