反应详情

In a round-bottomed flask, 4-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid (80 mg, 0.13 mmol) was dissolved in dichloromethane (0.7 ml) and trifluoroacetic acid (0.40 ml, 5.2 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.7 ml) and ethylenediamine (0.53 ml, 7.85 mmol) was added. The reaction was stirred at room temperature for 1 h then diluted with water and acidified with 1 M HCl then conc. HCl to pH=˜4. The resulting suspension was filtered and washed with hot water and ethyl acetate and the product was dried under high vacuum to provide 27 mg (41%) of 4-[3-(7-tert-butylcarbamoyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-5-difluoromethoxy-indazol-1-yl]-butyric acid as a brown powder. MS: (M+Na)+=509; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 9.09 (s, 1H), 8.39 (s, 1H), 8.22 (d, J=2.0 Hz, 1H), 7.86-7.92 (m, 2H), 7.42 (dd, J=9.1, 2.3 Hz, 1H), 7.21 (t, J=74.3 Hz, 1H), 4.59 (t, J=6.8 Hz, 2H), 2.26-2.33 (m, 2H), 2.08-2.19 (m, 2H), 1.51 (s, 9H).

1. concentrationthen concentrated
2. dissolutionThe residue was dissolved in dichloromethane (0.7 ml)
3. stirringThe reaction was stirred at room temperature for 1 h
4. filtrationThe resulting suspension was filtered
5. washwashed with hot water and ethyl acetate
6. customthe product was dried under high vacuum