反应详情

In a round-bottomed flask, 2-(5-chloro-indazol-1-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 (51 mg, 0.08 mmol) was dissolved in dichloromethane (0.5 ml) and trifluoroacetic acid (0.25 ml, 3.24 mmol) was added. The yellow reaction mixture was stirred at room temperature for 2.5 h then concentrated. The residue was dissolved in dichloromethane (0.5 ml) and ethylenediamine (0.33 ml, 4.89 mmol) was added. The reaction was stirred at room temperature for 1.5 h then quenched with water and extracted with EtOAc (2×30 ml). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over silica gel with EtOAc/hexanes (gradient 0-100% EtOAc) followed by trituration with EtOAc/hexanes (1:1) to provide 22 mg (52%) of 2-(5-chloro-indazol-1-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 yellow solid. MS: (M+H)+=503; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 13.01 (br. s., 1H), 9.10 (s, 1H), 8.94 (dd, J=8.9, 5.1 Hz, 1H), 8.54 (d, J=0.8 Hz, 1H), 8.51 (d, J=6.8 Hz, 1H), 8.29 (d, J=8.3 Hz, 1H), 8.07 (d, J=1.9 Hz, 1H), 7.56 (t, J=6.6 Hz, 1H), 4.92-5.02 (m, 1H), 3.70-4.06 (m, 2H), 3.09-3.68 (m, 3H), 1.50-2.08 (m, 4H), 1.20-1.39 (m, 1H), 0.31-0.61 (m, 4H).

1. concentrationthen concentrated
2. dissolutionThe residue was dissolved in dichloromethane (0.5 ml)
3. stirringThe reaction was stirred at room temperature for 1.5 h
4. customthen quenched with water
5. extractionextracted with EtOAc (2×30 ml)
6. washThe combined organic layers were washed with water and brine
7. dry with materialthen dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by chromatography over silica gel with EtOAc/hexanes (gradient 0-100% EtOAc)