反应详情

温度

25 °C

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-oxo-2-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)ethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (75.9 mg, 103 μmol) in dichloromethane (5 mL) under Ar, trifluoroacetic acid (744 mg, 0.50 mL, 6.52 mmol) was added at 25° C. After 96 h, the reaction was concentrated in vacuo and stirred in a mixture of dichloromethane/methanol/NH3OH (3:2:0.25, 5.25 mL) at 25° C. After 2.5 h, the material was concentrated and dried in vacuo (200 mTorr, 25° C.) to give a yellow solid. The solid was purified by chromatography (silica, 12 g Analogix column, 10-100% ethyl acetate in hexanes, gradient over 1 h) to give a yellow oil. The oil was dissolved in ethanol (4.5 mL, 200 proof) and cooled to 4° C. The precipitated solid was isolated by filtration and dried in vacuo (100 mTorr, 40° C.) to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-oxo-2-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)ethyl)-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (36.2 mg, 54.1 μmol, 53%) as a yellow solid. MS (M)'=609; 1H NMR (DMSO-d6) δ: 12.84 (d, J=3.0 Hz, 1H), 9.03 (s, 1H), 8.40 (d, J=3.0 Hz, 1H), 8.21 (d, J=2.3 Hz, 1H), 7.89 (s, 1H), 7.77 (d, J=9.0 Hz, 1H), 7.39 (dd, J=2.3, 9.0 Hz, 1H), 7.20 (t, J=74.5 Hz, 1H), 5.66 (s, 2H), 3.64 (br. s, 2H), 3.47 (br. s, 2H), 3.29 (q, J=10.3 Hz, 2H), 2.77 (br. s, 2H), 2.64 (br. s, 2H), 1.51 (s, 9H).

1. concentrationthe reaction was concentrated in vacuo
2. waitAfter 2.5 h
3. concentrationthe material was concentrated
4. customdried in vacuo (200 mTorr, 25° C.)
5. customto give a yellow solid
6. customThe solid was purified by chromatography (silica, 12 g Analogix column, 10-100% ethyl acetate in hexanes, gradient over 1 h)
7. customto give a yellow oil
8. temperaturecooled to 4° C
9. customThe precipitated solid was isolated by filtration
10. customdried in vacuo (100 mTorr, 40° C.)