Ethanol → 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(6-methylamino-pyridin-3-yl)-cyclopropyl]-amide

Temperature

160 °C

A pressure tube charged with 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(6-bromo-pyridin-3-yl)-cyclopropyl]-amide (0.200 g, 0.442 mmol), 33% methylamine in ethanol (0.250 mL, 1.99 mmol) in N-methylformamide (1 mL) is heated at 160° C. After 36 hours, the reaction is cooled to room temperature and diluted with ethyl acetate (20 mL) and water (20 mL). Phases are separated and the aqueous layer is extracted with ethyl acetate (3×20 mL). The combined organic layers are washed with saturated aqueous ammonium chloride (3×100 mL), saturated aqueous sodium bicarbonate (100 mL), brine (100 mL), dried over MgSO4, filtered and concentrated. The residue is purified by silica gel chromatography eluting with 0-15% methanol in dichloromethane to afford the title compound as a solid.

1. temperaturethe reaction is cooled to room temperature
2. customPhases are separated
3. extractionthe aqueous layer is extracted with ethyl acetate (3×20 mL)
4. washThe combined organic layers are washed with saturated aqueous ammonium chloride (3×100 mL), saturated aqueous sodium bicarbonate (100 mL), brine (100 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue is purified by silica gel chromatography
9. washeluting with 0-15% methanol in dichloromethane

ORD record

ord-d05bfbded6274c92a5e8be1e75ce60fc

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056858B2