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. for 18 h 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 and purified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane, 15 min gradient). 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, 81.3%) as a white solid. MS (M+H)+=367; 1H NMR (300 MHz, DMSO-d6) δ ppm 12.68 (m, 1H), 8.91 (s, 1H), 8.31 (s, 1H), 8.04 (d, J=8.31 Hz, 1H), 4.17-4.26 (m, 1H), 3.75 (s, 3H), 2.92 (t, J=6.42 Hz, 2H), 1.52 (t, J=6.42 Hz, 2H), 1.37 (s, 2H), 1.22 (d, J=6.42 Hz, 6H), 1.01 (s, 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
5. custompurified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane, 15 min gradient)
6. additioncyclohexane added
7. customThe solid was separated
8. customby decanting the mother liquors
9. customdried