反应详情

To a solution of 2-(5,6-dichloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (130 mg, 0.19 mmol) in CH2Cl2 (4 mL) was added TFA (2.0 mL, 26.0 mmol). The reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was redissolved in CH2Cl2 (4 mL) and ethylenediamine (0.4 mL, 5.92 mmol) was added. The reaction mixture was stirred at room temperature for 0.5 h then quenched with water and extracted with CH2Cl2 (3×). The combined organics were concentrated. The residue was purified by silica gel chromatography with 0% to 4% MeOH/CH2Cl2 (0.5% NH4OH) followed by trituration with Et2O to afford a white solid. This solid was further purified by recrystallization from MeOH/EtOAc to afford 22 mg of 2-(5,6-dichloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a white solid. MS: (M+Na)+=573; 1H NMR (DMSO-d6,300 MHz): δ (ppm) 12.92 (br. s., 1H), 9.14 (s, 1H), 8.88 (s, 1H), 8.69 (d, J=8.7 Hz, 1H), 8.46 (d, J=8.7 Hz, 1H), 8.24 (s, 1H), 4.93 (t, J=7.4 Hz, 1H), 4.18 (s, 3H), 3.45-3.94 (m, 3H), 3.15 (d, J=4.9 Hz, 2H), 1.35-1.91 (m, 5H), 0.51 (br. s., 4H).

1. concentrationthen concentrated
2. dissolutionThe residue was redissolved in CH2Cl2 (4 mL)
3. stirringThe reaction mixture was stirred at room temperature for 0.5 h
4. customthen quenched with water
5. extractionextracted with CH2Cl2 (3×)
6. concentrationThe combined organics were concentrated
7. customThe residue was purified by silica gel chromatography with 0% to 4% MeOH/CH2Cl2 (0.5% NH4OH)
8. customto afford a white solid
9. customThis solid was further purified by recrystallization from MeOH/EtOAc