反应详情

In a round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-amide (121 mg, 0.22 mmol) was dissolved in dichloromethane (1 ml) and trifluoroacetic acid (0.7 ml, 9.0 mmol) was added. The reaction mixture was stirred at room temperature for 2.5 h then concentrated. The residue was redissolved in dichloromethane (1 ml) and ethylenediamine (0.9 ml, 13.3 mmol) was added. The solution was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resultant suspension was filtered, rinsed with hot water and ethyl acetate then dried under high vacuum to provide 53 mg (58%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-amide as an off-white powder. MS: (M+H)+=413; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.83 (br. s., 1H), 9.14 (s, 1H), 8.75 (d, J=8.7 Hz, 1H), 8.42 (s, 1H), 8.16 (d, J=9.4 Hz, 1H), 7.95 (d, J=1.1 Hz, 1H), 7.36 (dd, J=8.7, 1.1 Hz, 1H), 4.78 (s, 1H), 4.17 (s, 3H), 4.03-4.16 (m, 1H), 1.22-1.28 (m, 6H), 1.16 (s, 3H).

1. concentrationthen concentrated
2. dissolutionThe residue was redissolved in dichloromethane (1 ml)
3. stirringThe solution was stirred at room temperature for 1 h
4. customthen quenched with water
5. additiondiluted with ethyl acetate
6. filtrationThe resultant suspension was filtered
7. washrinsed with hot water and ethyl acetate
8. customthen dried under high vacuum