反应详情

In a 10 ml round-bottomed flask, 2-[5-difluoromethoxy-1-(1-methyl-piperidin-4-yl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (crude from Step 2, 103 mg, 0.131 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 suspended in dichloromethane (0.7 ml) and ethylenediamine (0.53 ml, 7.85 mmol) was added. The light yellow suspension was stirred at room temperature for 1 h then water and ethyl acetate were added. The suspension was filtered and washed with hot water and ethyl acetate. The product collected was dried under high vacuum to provide 57 mg (83%) of 2-[5-difluoromethoxy-1-(1-methyl-piperidin-4-yl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow powder. MS: (M+H)+=498; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.08 (s, 1H), 8.38 (s, 1H), 8.20 (s, 1H), 7.86-8.00 (m, 2H), 7.39 (d, J=8.3 Hz, 1H), 7.19 (t, J=74.4 Hz, 1H), 4.67-4.83 (m, 1H), 2.95 (d, J=7.9 Hz, 2H), 2.27 (s, 3H), 2.12-2.32 (m, 4H), 2.00 (d, J=10.2 Hz, 2H), 1.50 (s, 9H).

1. concentrationthen concentrated
2. stirringThe light yellow suspension was stirred at room temperature for 1 h
3. filtrationThe suspension was filtered
4. washwashed with hot water and ethyl acetate
5. customThe product collected
6. customwas dried under high vacuum