反应详情

A flask was charged with the mono-TFA salt of 7-fluoro-3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (30.0 mg, 0.050 mmol), 1,1′-carbonyldiimidazole (48.7 mg, 0.30 mmol) and imidazole (17.0 mg, 0.25 mmol). The flask was put under an atmosphere of argon and 1,2-dichloroethane was injected (1 mL). The mixture was stirred 3 h at room temperature, warmed to 40° C. for 16 h, allowed to cool to room temperature and treated with (R)-methyl-benzylamine (0.1 mL). The reaction was stirred for 2 hours at room temperature and then diluted with 50% NaHCO3 (3 mL) and EtOAc (5 mL). The organic phase was separated, dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was dissolved in a mixture of DCM, TFA and triethylsilane (3:2:0.1 mL). After 2 h the reaction was filtered, concentrated under reduced pressure and the crude residue was purified by MS-directed reverse phase preparative-HPLC (C-18 stationary phase, eluting with a H2O/MeCN gradient with 0.1% TFA) to yield 1-[7-fluoro-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea as a white solid (9 mg, 0.019 mmol, 37%).

1. temperaturewarmed to 40° C. for 16 h
2. temperatureto cool to room temperature
3. stirringThe reaction was stirred for 2 hours at room temperature
4. customThe organic phase was separated
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. dissolutionThe resulting residue was dissolved in a mixture of DCM, TFA and triethylsilane (3:2:0.1 mL)
9. filtrationAfter 2 h the reaction was filtered
10. concentrationconcentrated under reduced pressure
11. customthe crude residue was purified by MS-directed reverse phase preparative-HPLC (C-18 stationary phase
12. washeluting with a H2O/MeCN gradient with 0.1% TFA)