反应详情

To a solution of 2-(6-chloro-1-ethyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (150 mg, 0.25 mmol) in CH2Cl2 (2 mL) was added TFA (0.75 mL). The reaction mixture was stirred at room temperature for 5 h then concentrated. The residue was redissolved in 10:90:0.5 MeOH/CH2Cl2/NH4OH (3 mL) and stirred at room temperature for 3 h. The reaction mixture was concentrated and the residue was purified by silica gel chromatography with 0% to 5% MeOH/EtOAc followed by trituration with MeOH to afford 88 mg (75%) of 2-(6-chloro-1-ethyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a white powder. MS: (M+Na)+=499; mp=248-255° C.; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.92 (br. s., 1H), 9.14 (s, 1H), 8.71 (d, J=8.7 Hz, 1H), 8.47 (dd, J=7.6, 3.4 Hz, 2H), 8.02 (s, 1H), 7.25 (d, J=8.7 Hz, 1H), 4.48-4.79 (m, 5H), 4.04-4.28 (m, 2H), 3.77-3.92 (m, 1H), 1.47 (t, J=7.2 Hz, 3H), 1.39 (dd, J=6.8, 4.5 Hz, 3H).

1. concentrationthen concentrated
2. dissolutionThe residue was redissolved in 10:90:0.5 MeOH/CH2Cl2/NH4OH (3 mL)
3. stirringstirred at room temperature for 3 h
4. concentrationThe reaction mixture was concentrated
5. customthe residue was purified by silica gel chromatography with 0% to 5% MeOH/EtOAc