反应详情

To a solution of 2-(6-tert-butyl-1-methyl-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 (129 mg, 0.21 mmol) in CH2Cl2 (2 mL) was added TFA (0.75 mL). The reaction mixture was stirred at room temperature for 4 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 to afford 74 mg (73%) of 2-(6-tert-butyl-1-methyl-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 light yellow powder. MS: (M+H)+=485; mp=180-195° C.; 1H NMR (CDCl3, 400 MHz): δ (ppm) 10.08-10.28 (m, 1H), 9.02-9.14 (m, 1H), 8.65 (d, J=7.1 Hz, 1H), 8.46 (d, J=8.6 Hz, 1H), 7.99-8.13 (m, 1H), 7.40-7.49 (m, 1H), 7.36 (s, 1H), 4.86-5.08 (m, 1H), 4.23-4.76 (m, 4H), 4.11 (s, 3H), 3.52-3.59 (m, 1H), 1.55-1.71 (m, 3H), 1.48 (s, 9H).

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