反应详情

In a round-bottomed flask, 2-(5-difluoromethoxy-1-pyridin-3-ylmethyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (124 mg, 0.20 mmol) was dissolved in dichloromethane (1 ml) and trifluoroacetic acid (0.62 ml, 8.05 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (1 ml) and ethylenediamine (0.81 ml, 12.0 mmol) was added. The yellow solution was stirred at room temperature for 1 h then quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was triturated with a small amount of diethyl ether containing a few drops of ethyl acetate to afford 83 mg (80%) of 2-(5-difluoromethoxy-1-pyridin-3-ylmethyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow powder. MS: (M+H)+=492; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.78 (br. s., 1H), 9.09 (s, 1H), 8.68 (d, J=1.9 Hz, 1H), 8.50 (dd, J=4.7, 1.3 Hz, 1H), 8.39 (s, 1H), 8.22 (d, J=2.3 Hz, 1H), 8.02 (d, J=9.4 Hz, 1H), 7.87 (s, 1H), 7.75 (d, J=7.9 Hz, 1H), 7.32-7.46 (m, 2H), 7.07 (t, J=74.0 Hz, 1H), 5.88 (s, 2H), 1.50 (s, 9H).

1. concentrationthen concentrated
2. dissolutionThe residue was dissolved in dichloromethane (1 ml)
3. stirringThe yellow solution was stirred at room temperature for 1 h
4. customthen quenched with water
5. extractionextracted with EtOAc (2×)
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 triturated with a small amount of diethyl ether containing a few drops of ethyl acetate