反应详情

To a stirred solution of tert-butyl 3-(3-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-5-(difluoromethoxy)-1H-indazol-1-yl)propyl(methyl)carbamate (0.1 g, 142 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL). After 15 h the mixture was concentrated in vacuo. 25 mL of a Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane was added. After 1 h, the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-5% methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-[5-difluoromethoxy-1-(3-methylamino-propyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (53 mg, 78%). MS (M+H)+=472; 1H NMR (DMSO-d6) δ: 9.30 (s, 1H), 8.61 (s, 1H), 8.43 (s, 1H), 8.08-8.14 (m, 2H), 7.59-7.68 (m, 1H), 7.12-7.71 (m, 1H), 4.82 (t, J=6.7 Hz, 4H), 3.54 (br. s., 3H), 2.27 (t, J=6.8 Hz, 2H), 1.73 (s, 9H).

1. concentrationAfter 15 h the mixture was concentrated in vacuo
2. addition10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane
3. additionwas added
4. concentrationthe mixture was concentrated in vacuo
5. customPurification by chromatography (silica, 24 g Analogix column, 0-5% methanol containing 10% ammonium hydroxide in dichloromethane)