反应详情

The less polar, diastereomer B of (3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester (66 mg, 126 μmol) isolated from Example 276 was dissolved in dichloromethane (5 mL) and treated with TFA (1.48 g, 1 mL, 13.0 mmol). After 18 h at room temperature the solvents were evaporated and the residue dissolved in dichloromethane/MeOH, adsorbed on silica gel and purified by chromatography (25 g column, 50 μm from Thomson, 0 to 5% MeOH containing 10% ammonium hydroxide) in dichloromethane, 20 min gradient) to give an off white residue that was dissolved in dichloromethane containing few drops of MeOH. Cyclohexane was added to promote solid formation. The precipitate was separated by decanting the mother liquor and dried under high vacuum to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclohexyl)-amide (diastereomer B) (18 mg, 33.7%) as a white solid. MS (M+H)+=424; 1H NMR (DMSO-d6) δ: 9.02 (s, 1H), 8.42 (s, 1H), 8.37 (d, J=8.7 Hz, 1H), 8.05 (d, J=7.9 Hz, 1H), 7.98 (s, 1H), 7.30 (d, J=10.2 Hz, 1H), 4.36 (br. s., 1H), 4.16 (s, 3H), 3.33 (br. s., 1H), 3.13 (br. s., 1H), 2.54 (br. s., 1H), 1.79 (br. s., 1H), 1.59-1.71 (m, 2H), 1.53 (d, J=9.4 Hz, 1H), 1.38 (s, 1H), 1.32 (s, 1H).

1. customAfter 18 h at room temperature the solvents were evaporated
2. dissolutionthe residue dissolved in dichloromethane/MeOH
3. custompurified by chromatography (25 g column, 50 μm from Thomson, 0 to 5% MeOH containing 10% ammonium hydroxide) in dichloromethane, 20 min gradient)
4. customto give an off white residue that
5. customThe precipitate was separated
6. customby decanting the mother liquor
7. customdried under high vacuum