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

HRID 2172980Notes

Reaction equation

HRID 2172980 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([C:8]2([NH:11][C:12]([C:14]3[C:15]4[CH:22]=[N:21][N:20]([C:23]5[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=5)[C:16]=4[CH:17]=[N:18][CH:19]=3)=[O:13])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:30][NH2:31].C(O)C>CNC=O.C(OCC)(=O)C.O>[CH3:30][NH:31][C:2]1[N:7]=[CH:6][C:5]([C:8]2([NH:11][C:12]([C:14]3[C:15]4[CH:22]=[N:21][N:20]([C:23]5[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=5)[C:16]=4[CH:17]=[N:18][CH:19]=3)=[O:13])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 702EthanolHCID 6329MethylamineHCID 52916799HCID 52916799, compound

Product 1

HCID 529174271-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(6-methylamino-pyridin-3-yl)-cyclopropyl]-amide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 31254N-MethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d05bfbded6274c92a5e8be1e75ce60fc
Source dataset
uspto-grants-2015_06
Patent number
US09056858B2

Reaction notes

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